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Review

Bright Side of Fusarium oxysporum: Secondary Metabolites Bioactivities and Industrial Relevance in Biotechnology and Nanotechnology

by
Sabrin R. M. Ibrahim
1,2,*,
Alaa Sirwi
3,
Basma G. Eid
4,
Shaimaa G. A. Mohamed
5 and
Gamal A. Mohamed
3,6
1
Preparatory Year Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia
2
Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
3
Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
4
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
5
Faculty of Dentistry, British University, Suez Desert Road, Cairo 11837, Egypt
6
Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
*
Author to whom correspondence should be addressed.
J. Fungi 2021, 7(11), 943; https://doi.org/10.3390/jof7110943
Submission received: 12 October 2021 / Revised: 1 November 2021 / Accepted: 6 November 2021 / Published: 8 November 2021
(This article belongs to the Section Fungal Cell Biology, Metabolism and Physiology)
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Versions Notes

Abstract

:
Fungi have been assured to be one of the wealthiest pools of bio-metabolites with remarkable potential for discovering new drugs. The pathogenic fungi, Fusarium oxysporum affects many valuable trees and crops all over the world, producing wilt. This fungus is a source of different enzymes that have variable industrial and biotechnological applications. Additionally, it is widely employed for the synthesis of different types of metal nanoparticles with various biotechnological, pharmaceutical, industrial, and medicinal applications. Moreover, it possesses a mysterious capacity to produce a wide array of metabolites with a broad spectrum of bioactivities such as alkaloids, jasmonates, anthranilates, cyclic peptides, cyclic depsipeptides, xanthones, quinones, and terpenoids. Therefore, this review will cover the previously reported data on F. oxysporum, especially its metabolites and their bioactivities, as well as industrial relevance in biotechnology and nanotechnology in the period from 1967 to 2021. In this work, 180 metabolites have been listed and 203 references have been cited.

1. Introduction

Fungi are eukaryotic microorganisms that settled mostly in all kinds of environments and have fundamental roles in maintaining the environmental balance [1,2]. It has been stated that only about 5% of 2.2 to 3.8 million different fungal species on earth have been taxonomically characterized [3,4]. Fungi have been considered as one of the wealthiest pools of natural metabolites with unique structural features and biodiversity that have a remarkable role in developing new drugs [1,2,3,5,6,7,8,9,10]. Some fungal metabolites are also highly toxic such as Aspergillus mycotoxin and aflatoxin B1, which affect human health when occurring in food products [8,9,11]. Therefore, it is important to unravel the metabolites of fungal species to prevent health risks, as well as to identify new potential bioactive compounds. Fusarium is a genus of filamentous fungi that includes many mycotoxin producers, agronomically important plant pathogens, and opportunistic human pathogens [12]. Its species are a widespread cosmopolitan group of fungi that are found in various habitats such as water, soil, or associated with plants [13,14]. They commonly colonize subterranean and aerial plant parts, either as primary or secondary invaders [15]. Many Fusarium species are spread out pathogens on crops in temperate and semi-tropical regions that produce a variety of mycotoxins, causing a reduction in yield and quality of crops, as well as animal and human health risks [16]. On the other hand, some species have the potential capacity to produce a great number of metabolites with remarkable chemical diversity and significant bioactivities [11,17,18,19,20,21,22,23,24,25,26]. Fusarium oxysporum is the most encountered and economically important species of this genus. It includes pathogenic (plant, human, and animal) and non-pathogenic strains that even possess bio-control activity against fungal pests and some insects [27]. It is one of the soil-borne pathogens that causes vascular wilt on many plants, which is characterized by various symptoms, including leaf epinasty, vascular browning, progressive wilting, defoliation, stunting, and plant death [28]. Its species complex consists of several formae speciales (f. sp.) that collectively infect more than one hundred hosts, leading to serious losses in crops such as tomato, melon, banana, and cotton [29]. In humans, F. oxysporum causes invasive infections in immuno-compromised patients and it is commonly found in onychomycosis [30,31]. Many studies revealed that F. oxysporum showed a remarkable capacity to yield diverse classes of secondary metabolites such as alkaloids, jasmonates, anthranilates, cyclic peptides, cyclic depsipeptides, xanthones, quinones, and terpenoids with various activities such as phytotoxicity, antimicrobial, cytotoxicity, insecticidal, antioxidant, and antiangiogenic. Additionally, F. oxysporum possessed significant industrial and biotechnological values as a wealthy source of diverse enzymes with wide applications such as cutinases, nitrilases, glycoside hydrolases (e.g., fucosidase, α-galactopyranosidases, and xylanases), fructosyl amino acid oxidase, laccases, lipoxygenase, nitric oxide reductase, decarboxylases, keratinase, phospholipase B, and triosephosphate isomerase [32,33,34,35,36,37,38,39,40,41,42]. Further, F. oxysporum is widely employed for the synthesis of different types of metal nanoparticles that could have various biotechnological, pharmaceutical, industrial, and medicinal applications [43,44,45,46,47,48,49,50,51,52,53,54,55]. The intensive literature search revealed the lack of review articles that deal with F. oxysporum particularly the bright side of this economically valuable fungus. The current review summarized the published data regarding secondary metabolites reported from this fungus and their bioactivities. Additionally, the research progress on F. oxysporum, including industrial, biotechnological, and nanotechnological applications has been discussed. The studies that have appeared in literature from 1967 to 2021 are reported. The chemical classes, structures, molecular formulae and weights, hosts, places, and bioactivities of the reported metabolites have been listed (Figures 1–19 and Table 1 and Table 2). Moreover, the reported biosynthetic pathways of some major F. oxysporum metabolites have been included (Schemes 1–3). The aim of this work is to focus on the interests of biologists, chemists, and natural product researchers on the area of pharmaceutical drug leads development of the reported metabolites. Besides, the covered data of industrial relevance in biotechnology and nanotechnology have been discussed. The literature search for this work was performed through a computer search of data on Web of Knowledge, ScienceDirect, SCOPUS, Taylor & Francis, Wiley Online Library, Springer, PubMed, JACS, and Google Scholar.

2. Nanotechnological Applications

Nanotechnology holds promise in the medicine, agriculture, and pharmaceutical industries [112]. Natural nanostructures have gained more attention due to the wide spectrum of bioactivities and fewer animals, humans, and environmental toxicity. The microbial synthesis of nanoparticles is an approach of green chemistry that combines both nanotechnology and microbial biotechnology [113]. Metals nanoparticles are increasingly used in various biotechnological, pharmaceutical, and medicinal applications, including drug delivery, gene transfer, insect-pests management in agriculture, and bioelectronics devices fabrication, as well as antibacterial agents towards many pathogenic bacteria, including the MDR (multidrug-resistant) strains [114,115,116].

2.1. Metal Nanoparticles

Several studies reported the synthesis and characterization of metal nanoparticles (NPs) using F. oxysporum, as well as their bioactivities. Additionally, some studies dealt with optimizing the conditions for the synthesis of NPs by F. oxysporum, including temperature, media, pH, salt concentration, light intensity, the volume of filtrate, and biomass quantity [44,47,50,51,54,55]. Marcato et al., synthesized AgNPs (silver nanoparticles) using F. oxysporum. The incorporation of these NPs in cotton cloth was found to exhibit a bactericidal effect towards S. aureus, leading to its sterilization [50]. Ishida et al., synthesized AgNPs using F. oxysporum aqueous extract that showed significant antifungal potential towards Cryptococcus and Candida (MIC values ≤ 1.68 µg/mL) [51]. Moreover, it was found that the biosynthesized AgNPs by two F. oxysporum isolates exhibited higher antibacterial potential towards human-pathogenic bacteria; E. coli, Proteus vulgaris, S. aureus, and K. pneumonia than the used antibiotics. These AgNPs could be favorable antibacterial agents, especially towards MDR bacteria [44]. Ahmed et al., synthesized AgNPs using F. oxysporum, which inhibited some MDR species of Staphylococcus and Enterobacteriaceae (conc. 50% v/v), as well as Candida krusei and C. albicans, suggesting that they might be potential alternatives to antibiotics [46]. The in-silico and in-vitro studies demonstrated the immense antibacterial potential of F. oxysporum’s AgNPs against P. aeruginosa and E. coli [45]. The AgNPs synthesized using nitrate reductase purified from F. oxysporum IRAN-31C showed potent antimicrobial potential towards a wide array of human pathogenic bacteria and fungi in the disk diffusion method [117]. A study by Ballottin et al., revealed that the cotton fibers impregnated with biogenic AgNPs synthesized from F. oxysporum filtrate solution possessed potent antimicrobial potential even after repeated mechanical washing cycles. This might highlight the potential use of biogenic AgNPs as an antiseptic in textiles for medical applications [118].
Moreover, a study by Hamedi et al., revealed that the existence of ammonium lowered the productivity of AgNPs using F. oxysporum cell-free filtrate and prohibited the nitrate reductase enzyme secretion [119]. Longhi et al., reported that the combination of AgNPs synthesized using F. oxysporum with FLC (fluconazole) reduced the MIC of FLC around 16 to 64 times towards planktonic cells of C. albicans and induced a significant dose-dependent inhibition of both initial and mature biofilms of FLC-resistant C. albicans. Therefore, these AgNPs could represent a new strategy for treating FLC-resistant C. albicans infections [49]. Additionally, the combination of simvastatin with these AgNPs demonstrated antibacterial activity towards E. coli-producing ESBL (extended-spectrum β-lactamase) and MRSA (methicillin-resistant S. aureus). This could be a great future alternative in bacterial infection control, where smaller doses of these AgNPs are required with the same antibacterial activity [120]. Besides, its combination with polymyxin B showed a 16-fold reduction of the MIC of polymyxin B and decreased carbapenem-resistant Acinetobacter baumannii viability with additive and synergic effects, as well as significantly reduced cytotoxicity towards mammalian Vero cells, indicating its pharmacological safety [121]. The AgNPs synthesized with F. oxysporum f.sp. pisi were found to have moderate adulticidal potential on Culex quinquefasciatus (vector of filariasis) (LC50 0.4, LC99 4.8, and LC90 4 μL/cm2) after 24 h exposure [122]. The synthesized AgNPs using F. oxysporum aqueous extract had anticancer potential towards MCF7 (IC50 14 µg/mL) that was characterized using CLSM (confocal laser scanning microscopic) technique [123]. Bawskar et al. stated that the biosynthesized AgNPs using F. oxysporum possessed more potent antibacterial potential towards E. coli and S. aureus than chemo-synthesized AgNPs that may be due to the protein capping and their mode of entry into the bacterial cell, which encouraged biosynthetic method over the chemosynthetic one in AgNPs synthesis [124]. Two types of AgNPs, phyto-synthesized and myco-synthesized NPs were biosynthesized by AgNO3 reduction with Azadirachta indica extract and F. oxysporum cell filtrate, respectively that possessed lower cytotoxic potential on C26 and HaCaT cell lines as compared with citrate coated AgNPs [125]. Santos et al. proved that F. oxysporum-biosynthesized AgNPs without pluronic F68 (stabilizing agent) had high antibacterial potential towards E. coli, P. aeruginosa, and S. aureus. On the contrary, chemo-synthesized AgNPs exhibited synergism in antibacterial activity in the presence of pluronic F68 [126]. Streptococcus agalactiae is an important cause of invasive diseases, mainly in newborns, pregnant women, and elderly individuals [127]. The combination of F. oxysporum-produced AgNPs (AgNPbio) and eugenol led to a remarkable synergistic effect and significant reduction of the MIC values of both eugenol and AgNPbio towards planktonic cells of S. agalactiae [127]. Thakker et al., reported the synthesis of GNPs (gold nanoparticles) using F. oxysporum f. sp. cubense JT1 that showed antibacterial potential versus Pseudomonas sp. [128]. Moreover, the conjugated GNPs with tetracycline demonstrated powerful antibacterial activity against Gram-negative and -positive bacteria in comparison to tetracycline and free GNPs. Therefore, tetracycline conjugation with these GNPs enhanced the antibacterial potential, which may have significant therapeutic applications [129]. Yahyaei and Pourali studied the conjugation of GNPs with chemotherapeutic agents such as paclitaxel, tamoxifen, and capecitabine. Moreover, the cytotoxic effect of conjugated GNPs was assessed towards MCF7 and AGS cell lines, using MTT assay. Unlike the paclitaxel conjugated GNPs, the tamoxifen and capecitabine conjugated GNPs revealed no toxic effects due to their low half-lives and deactivation [130]. Further, Syed and Ahmad reported the synthesis of stable extracellular platinum nanoparticles, using F. oxysporum [131]. CdSe (cadmium/selenium) quantum dots are often used in industry as fluorescent materials. Kumar et al., and Yamaguchi et al., reported the synthesis of highly luminescent CdSe quantum dots by F. oxysporum [132,133]. In 2013, Syed and Ahmad synthesized highly fluorescent CdTe quantum dots using F. oxysporum at ambient conditions by the reaction with a mixture of TeCl4 and CdCl2. These nanoparticles exhibited antibacterial potential towards Gram-negative and -positive bacteria [53]. Riddin et al., analyzed the biosynthesized platinum (Pt) nanoparticles by F. oxysporum f. sp. lycopersici at both intercellular and extracellular levels. It was found that only the extracellular nanoparticle production was proved to be statistically significant with a yield of 4.85 mg/L [134].

2.2. Metal Sulfide Nanoparticles

In addition, Q-state CdS NPs were biosynthesized by the reaction of aqueous CdSO4 solution with F. oxysporum [135]. The chemically-synthesized CdSQDs inhibited E. coli cell proliferation in a dose-dependent manner, unlike the biogenic CdSQDs synthesized by F. oxysporum f. sp. lycopersici, which showed an antibacterial potential only at high concentration. Additionally, only the biogenic CdSQDs showed no inhibition on seed germination after incubation of biogenic and chemical CdSQDs with Lactuca sativa seeds [43]. Bi2S3 (bismuth sulfide) NPs have significantly varied applications, including photodiode arrays, photovoltaic materials, and bio-imaging. Uddin et al., synthesized a highly fluorescent, natural protein capped Bi2S3NPs by subjecting F. oxysporum to bismuth nitrate penta-hydrate, along with sodium sulfite under ambient conditions of pressure, temperature, and pH. It was found that they were fundamentally much more fluorescent than fluorophores (toxic fluorescent chemical compounds), which are largely utilized in immunohistochemistry, imaging, and biochemistry [48].

2.3. Metal Oxide Nanoparticles

It was reported that F. oxysporum might have vast commercial implications in low-cost, room-temperature, ecofriendly syntheses of technologically significant oxide nanomaterials from available potentially cheap naturally raw materials [136]. F. oxysporum rapidly bio-transformed the naturally occurring amorphous biosilica in rice husk into crystalline silica NPs. This could lead to an economically viable and energy-conserving green approach toward the large-scale synthesis of oxide nanomaterials [136]. Moreover, the mesophilic F. oxysporum bioleached Fly-ash at ambient conditions produced highly stable, crystalline, fluorescent, water-soluble, and protein-capped silica nanoparticles [52]. It was found that F. oxysporum enriched zirconia in zircon sand by a process of selective extracellular bioleaching of silica nanoparticles. It was proposed that the fungal enzymes specifically hydrolyzed the silicates in the sand to form silicic acid, which on condensation by certain other fungal enzymes resulted in silica nanoparticles synthesis at room temperature [136]. A water dispersible and thermo-stable Ag/Ag2O NPs were produced from silver oxide micro-powder using F. oxysporum. These Ag/Ag2O NPs may become a potential candidate for enzyme-free glucose determination and exhibited catalytic potency for MB (methylene blue) degradation in presence of NaBH4 (reducing agent). Additionally, they showed an excellent antimicrobial potential against A. niger and B. subtilis [137].

3. Biotechnological and Industrial Relevance of F. oxysporum

F. oxysporum is a wealthy source of enzymes with significant biotechnological and industrial potential. In various studies, F. oxysporum demonstrated a remarkably high enzymatic performance and the ability to degrade different biomasses. Herein, the reported enzymes from F. oxysporum and their industrial and biotechnological applications are highlighted.

3.1. F. oxysporum Enzymes and Their Applications

3.1.1. Glycoside Hydrolases

Cellulases are accountable for cellulose hydrolysis, including β-1,4-endoglucanase, cellobiohydrolase, and β-glucosidases (BGL), which catalyze the hydrolysis of aryl- and alkyl-β-glucosides, as well as oligosaccharides and diglucosides [1,3,5]. Cellulases’ preparations have been added to the ruminant animals’ diets to stimulate feed processing and fiber digestion to increase the extent and rate of digestion [138]. Zhao et al., purified extracellular BGL from F. oxysporum that had high acid stability (pH 3) and cellobiose hydrolytic activity relative to Celluclast® (commercial cellulase). Its supplementation also released more reducing sugars (330 mg/g substrate) from cellulose, in comparison to Novozymes (commercial BGL, 267 mg/g substrate) under simulated gastric conditions. Thus, it could be a good source for a new commercial BGL for improving the feed and food quality in the animal feed industry and could be used in combination with Celluclast for industrial applications that required degradation of cellulose at acidic pH [37].
Fucose is a low abundant deoxy-hexose sugar, usually attached to the non-reducing ends of oligolipids, oligosaccharides, and other glycoconjugates (e.g., immunoglobulins, glycoproteins, blood group substances, and mucins). Besides, it is a component of marine algal polysaccharides, human milk oligosaccharides, and plant gums [139]. FUC (α-L-fucosidase) a glycoside hydrolase, catalyzes the breakdown of the terminal α-L-fucosidic bonds. It has remarkable roles in various bioprocesses, and it is used as a marker for hepatocellular carcinoma detection and structural analyses of complex natural products [140]. F. oxysporum produced FUC in large amounts through induction by L-fucose. This enzyme hydrolyzed p-nitrophenyl α-L-fucoside (synthetic substrate) like marine gastropod and mammalian enzymes, thus it could replace these enzymes. It had beneficial use as an analytical tool for the structural elucidation of complex carbohydrates and oligosaccharides [41]. Additionally, Yano et al., purified a novel FUC from F. oxysporum culture broth. Besides nitrophenyl compounds, this enzyme had a novel substrate specificity. It could hydrolyze porcine mucin and blood group substances [42].
α-D-Galactopyranosidase (GPase) is a glycoside hydrolase that hydrolyzes the α-galactopyranosyl linkages at non-reducing ends of sugar chains. They are utilized for various applications, including eliminating non-digestible oligosaccharides such as stachyose in legume products and soybean, improving the digestibility of animal feed, and increasing the yield and quality of sucrose in sugar refineries [141]. FoAP1 and FoAP2 are two bifunctional enzymes that were isolated and characterized from the culture supernatant of F. oxysporum 12S, possessing GPase (α-D-galactopyranosidase)/APase (β-L-arabinopyranosidase) activities in a ratio 1.7 and 0.2, respectively using PNP-α-D-Galp (para-nitrophenyl α-D-galactopyranoside) and PNP-β-L-Arap (para-nitrophenyl α-l-arabinopyranoside) as substrates [38]. A novel GPase, FoGP1 was purified from F. oxysporum, exhibiting degrading activity with terminal α-1,3-galactosyl linkages in gum Arabic side chains. Therefore, it might be used for improving gum Arabic physical properties, which is an industrially important polysaccharide used as a coating agent and an emulsion stabilizer [34].
Xylan is one of the most abundant carbohydrates on earth. Its complete degradation is accomplished by the action of various enzymes such as β-D-xylosidases and endo-β-1,4-xylanases. Alconada and Martínez characterized extracellular β-xylosidase and endo-1,4-β-xylanase from F. oxysporum f. sp. melonis, growing in a medium containing oat spelt xylan. The latter had a high affinity towards oat spelt xylan [142]. Additionally, FoXyn10a, new GH10 xylanase was purified and structurally characterized from F. oxysporum [143]. Anasontzis et al., reported that the constitutive homologous overexpression of the endo-xylanase in F. oxysporum increased ethanol production during CBP of lignocellulosics [144]. Xyn11a is an endo-1,4-β-xylanase gene from F. oxysporum, belonging to the fungal glycosyl hydrolase family 11 (GH-11) that was cloned and expressed in Pichia pastoris. Recombinant P. pastoris possessed efficient xylanase secreting potential and a high level of enzymatic activity under methanol induction [145]. Gómez et al., identified Xyl2, an endo-β-1,4-xylanase from F. oxysporum. It was highly active at alkaline pH and its immobilization on certain supports significantly increased its thermal stability. Together, these properties rendered Xyl2, an attractive biocatalyst for the sustainable industrial degradation of xylan [146]. Najjarzadeh et al., compared xylanase production by different inducers, such as lactose, sophorose, xylooligosaccharides, and cellooligosaccharides in F. oxysporum f. sp. lycopersici. It was found that xylooligo-saccharides were more effective than other substrates at the induction of β-xylosidases and endoxylanases. Moreover, xylotetraose, xylohexaose, and xylobiose were the best inducers of endoxylanase, extracellular β-xylosidase, and cell-bound β-xylosidase, respectively [147].

3.1.2. Nitrilases

Microbial nitrilases are biocatalysts of remarkable organic importance in terms of nitrile conversion. Nitrile compounds include aromatic and simple aliphatic metabolites, cyano-lipids, and cyano-glucosides which serve as key intermediates and compounds in various biochemical pathways [148]. Processes involving enzymatic conversion of nitrile substrates to higher value amides and carboxylic acid groups are preferred over the chemical synthesis for their production of fewer harmful reaction by-products and greater reaction specificity [149]. Industrial application of nitrile-converting enzymes includes acrylamide and nicotinamide production [35]. The newly isolated nitrilase from F. oxysporum f. sp. lycopercisi ED-3 strain had a wide substrate specificity toward ortho-substituted heterocyclic, aliphatic, and aromatic nitriles and had optimal activity at temperature 50 °C and pH 7.0 [35].

3.1.3. Nitric Oxide Reductases

Denitrification is a substantial process in the nitrogen cycle, which involves the reduction of NO−2 and/or NO3− to either N2O or N2. This process can be performed by many bacteria, as well as fungi through a series of consecutive metallo- enzyme-catalyzed chemical reactions [150]. It is a reversible process of nitrogen fixation, where it carries back the fixed N2 to the atmosphere. It was found that the main source of global N2O emissions is the microbial activities of denitrification and nitrification [151]. Therefore, controlling microbial denitrification is most important for N2O emission reduction [152]. It was reported that F. oxysporum exhibited a distinct denitrifying potential that resulted in the anaerobic evolution of N2O from NO−2 and NO3− [153]. Further, a nitric oxide reductase (NOR), cytochrome P450nor, belonging to P450 superfamily was purified from F. oxysporum, which exhibited remarkable NO reduction potential [36,150,152]. It showed a unique bio-function compared with other usual P450s. While the usual P450s are involved in metabolizing various biological substances through mono-oxygenation reaction using O2, P450nor catalyzed the NO reduction but not the mono-oxygenation [150,154]. Shoun and Tanimoto described a heme-thiolate protein or P450 from F. oxysporum that was involved in the NO (nitrogen monoxide) reduction to N2O (dinitrogen oxide) [153]. In contrast to other bacterial cytochrome bc-containing NO reductases, it did not need a flavoprotein for electron transfer from NADH to the heme, but it utilized NADH directly for the reduction process [155]. Additionally, Daiber et al., identified P450nor (cytochrome P450 NADH-NO), a heme-thiolate protein that catalyzed the reduction of two NO molecules to N2O. P450nor was observed to have a remarkable role in protecting the fungus from NO inhibition of mitochondria [156].

3.1.4. Cutinases

Esters having a chain of fewer than 10 carbon atoms are used as flavor compounds in the pharmaceutical, cosmetic, and food industries [157]. Natural synthesis of flavor compounds takes place either by enzymatic bioconversion or by microorganisms, the former path was found to be an easier and more suitable method [157]. The high demand of various industries for fatty acid ester leads to possible growth of the market to $2.44 billion by 2022, from $1.83 billion in 2014 [33,158]. Enzyme immobilization increases their stability and allows their easy separation from the reaction and reuse to overcome the drawbacks of utilizing enzymes such as low operational or storage stability, and/or heat and organic solvent sensitivity [159]. The imFocut5a a CLEAs (cross-linked enzyme aggregates) was produced from a crude F. oxysporum cutinase preparation. This immobilized cutinase possessed a remarkable thermo-stability and was able to synthesize butyl butyrate (pineapple flavor) at a high yield of bioconversion (99%) through the trans-esterification of vinyl butyrate with butanol. This bioconversion presented an eco-friendly and sustainable production of natural flavor compounds, underpinning its industrial potential for use in food bioprocesses [33]. FoCut5a, a cutinase was purified from F. oxysporum and expressed either in the periplasm or cytoplasm of E. coli BL21. It could hydrolyze PET (polyethylene terephthalate) and synthetic polymers. Therefore, it could be used in industrial applications as a biocatalyst for the eco-friendly treatment of synthetic polymers [160].

3.1.5. Fructosyl Amino Acid Oxidases

Glycation is the non-enzymatic glycosylation of proteins due to the condensation of reducing sugars such as glucose with the proteins (α- or ε-amino groups) to form a Schiff’s base [161]. Glycation leads to browning of foods during long-term storage, which represents a problem in the food industry [39]. Glycation of hemoglobin, blood proteins, and albumin was found to be enhanced in diabetic patients. Glycated proteins, particularly glycated hemoglobin A1c, are important markers for assessing the effectiveness of anti-diabetic agents. Fructosyl amino acid oxidase (FAOD) based assays have become an attractive alternative to conventional detection methods for measuring glycated proteins [161]. Sakai et al., purified FLO (fructosyl lysine oxidase) from F. oxysporum S-lF4 that acted against fructosyl poly L-lysine. FLOD could be used for measuring glycated proteins such as glycated albumin in the serum [39].

3.1.6. Lipoxygenase

Lipoxygenase (LOX) is a dioxygenase that catalyzes the hydro-peroxidation of polyunsaturated fatty acids such as arachidonic and linoleic acids [162]. It is expressed in epithelial, tumor, and immune cells that have various physiological functions such as skin disorders, inflammation, and tumorigenesis [163]. Bisakowski et al., extracted and purified LOX from F. oxysporum that shared many of the characteristics with LOXs reported from other sources such as substrate specificity, pH, enzyme inhibition, activation, and other kinetic studies [40].

3.1.7. Laccases

Laccases are belonging to oxidoreductases that catalyze the O2 reduction to H2O with simultaneous organic substrates oxidation. They oxidize phenolic substrates but are also able to oxidize bigger or non-phenolic substrates by LMS (laccase-mediator system), where a small phenolic compound acts as a mediator [164]. Additionally, they have been reported as potential lignin-degrading enzymes and as solubilizing agents [165,166]. They have attracted great interest because of their wide applications in diverse biotechnological and industrial fields such as textile dye decolorization, pulp bleaching, organic synthesis, bioremediation, and detoxification of environmental pollutants, delignification, or biofuel production [1,3,5].
Kwiatos et al., expressed F. oxysporum Gr2 laccase in Saccharomyces cerevisiae and engineered it for getting higher effect against 2,6-dimethoxyphenol and higher expression levels. The resulted laccase had a promising potential for different industrial uses such as solubilization of brown coal, which is a clean coal technology, aiming at converting lignite to its cleaner form [164]. In 2018, Kwiatos et al., reported that F. oxysporum LOCK-1134 isolated from brown coal, efficiently bio-solubilized lignite, producing liquefied products that had over 99% less Hg and 50% less sulfur than the crude coal. Additionally, its laccase was expressed in Pichia pastoris. The resulted novel laccase improved the biodegradation process in presence of LMS. It released fulvic and humic acids from liquefied coal. The latter are environmentally friendly fertilizers that possessed a stimulating influence on crop growth [165].

3.1.8. Aromatic Carboxylic Acid Decarboxylases

The non-oxidative aromatic carboxylic acid decarboxylases catalyze the reversible decarboxylation of phenolic carboxylic acids. Therefore, they are useful biocatalysts for preparing high-value phenolic compounds by the decarboxylation of phenolic carboxylic acids derived from lignin, which opens up a new prospect for high-value utilization of the world second most abundant organic substance [167,168]. Song et al., characterized 2,3-DHBD_Fo, a 2,3-dihydroxybenzoic acid decarboxylase from F. oxysporum that possessed a relatively high catalytic decarboxylation efficiency for DHBA (2,3-dihydroxybenzoic acid) and catechol, hence it had a different substrate spectrum from other benzoic acid decarboxylases [167].

3.1.9. Keratinases

Keratins are complex proteins that formed of β-sheets and α-helix structures. They are commonly found in agro-industrial residues such as swine hair and chicken feathers. Keratinous wastes are treated in non-eco-friendly ways, including landfills and incinerators [169,170]. F. oxysporum isolated from chicken feathers showed potential for keratinase production that had the highest degradation percentage (59.20% w/w) in swine hair [169].

3.1.10. Phospholipase B

Phospholipase B (PLB) hydrolyzes the phospholipid acyl groups to produce fatty acids and phosphoglycerates [171]. PLB is utilized to produce beneficial phospholipid derivatives, reduce food’s cholesterol content, and refine vegetable oils, especially in terms of crude oil degumming [172]. Su et al., characterized a putative lipase from F. oxysporum NCBI-EGU84973.1 that was expressed in P. pastoris and classified as a PLB. It had phospholipids hydrolyzing potential greater than its lipase capacity where it hydrolyzed the fatty acyl ester bond at the sn-1 and -2 positions of the phospholipids and reduced the oil phosphorus contents. This proved the potential industrial use of this PLB in oil degumming applications [172].

3.1.11. Triosephosphate Isomerase

TPI (triosephosphate isomerase) is a glycolysis enzyme that catalyzes the reversible isomerization between DHAP (dihydroxyactetone-3-phosphate) and GAP (glyceraldehyde-3-phosphate) [173]. Therefore, TPI is essential for pathogenic organisms to get the energy needed for survival and infection. Hernández-Ochoa et al., isolated, cloned, and overexpressed Tpi gene from F. oxysporum isolated from a wild species collected from a bean crop. They purified FoxTPI recombinant protein that had the TPIs classical topology conserved in other organisms [14].

3.2. Applications of F. oxysporum

Biodiesel (biofuel) is obtained from renewable sources such as animal fat or vegetable oil by trans-esterification of triglycerides to give fatty acid alkyl esters [174]. It is used as a full or partial substitute for petrol diesel in combustion engines [175]. Its production attracts attention worldwide due to the environmental benefits such as biodegradation that reduced the emission of sulfur and aromatic hydrocarbons during fuel combustion and decreased emission of CO2, CO, and particulate materials. The accumulated lipids in microorganisms such as algae, fungi, and bacteria are mainly triacylglycerols (TAG) that are utilized as metabolites for biodiesel production [32]. F. oxysporum NRC2017 isolated from Egyptian soil had remarkable lipid producing capacity (55.2%). It showed the highest lipid accumulation 98.3 mg/g in the presence of baggase and its fatty acids were found to be suitable for biodiesel production based on GC analysis [32].
On earth, the most abundant source of biomass is lignocellulosic material that includes agricultural residues, grasses, wood, or any non-food-plant sources. Its microbial fermentation produces ethanol and other solvents that represent an alternative path for wastes treatment and production of fuel additives and chemical feedstocks. F. oxysporum was found to have the potential for converting D-xylose, as well as cellulose to ethanol in a one-step process, indicating its capacity for ethanol production [176].
Bioethanol production is a harsh operational process that needs potent biocatalysts. CBP (consolidated bioprocessing) is an economical and efficient method of manufacturing bioethanol from lignocellulose. CBP integrates the fermentation and hydrolysis steps into a single process, leading to a significant reduction in the steps of the biorefining process. Ali et al., reported that F. oxysporum had a high potential for CBP of lignocellulose to bioethanol and it could be a commercially competitive CBP agent [177]. It was observed a significant inter-strain divergence regarding the capacity of different F. oxysporum strains to produce alcohol from wheat straw [178]. Nait M’Barek et al., assessed the potential of F. oxysporum for bioethanol production from non-valorized OMW (olive mill waste) using CBP. It showed maximum bioethanol yield and production of 0.84 g/g and 2.47 g/L, respectively, indicating its importance as a bio-agent for single-pot local bio-refinery [179]. Moreover, F. oxysporum BN converted imidazolium-based ionic liquid (IL)-pretreated rice straw to bioethanol via CBP with 64.2% of the theoretical yield of 0.125 g ethanol/g rice straw [164]. It secreted a novel IL-tolerant cellulase that can direct the conversion of IL-pretreated lignocellulose residue to ethanol, which had a significant potential to bring a breakthrough in commercial ethanol production by the reduction of the overall cost [180].

4. Secondary Metabolites from F. oxysporum and Their Bioactivities

4.1. Anthranilates

Anthranilates are derivatives of anthranilic acid that constitute an important part of several bio-metabolites and serve as a scaffold for developing remarkable pharmaceuticals for the management of the pathogenesis and pathophysiology of diverse disorders. They possessed impressive bioactivates such as antiviral, antimicrobial, insecticidal, anti-inflammatory, anti-diabetic, and anticancer [181]. Compounds 1–21 are anthranilic acid derivatives that had been purified and characterized only from F. oxysporum f. sp. dianthi extracts using HPLC-, pyrolysis-, and HR-MS [56]. It was reported that the anthranilic acid derivatives are originated from 2 that is formed from benzoate and anthranilate [182]. Subsequently, it undergoes hydroxylation at C-2′ to produce dianthalexin, hydroxylation at C-4 to yield 3 or 5, and methylation to 9 or 8. Moreover, 20 and 19 are produced from 5 and 3 [56,183] (Scheme 1, Figure 1).

4.2. Fumonisins

Fumonisins are mycotoxins, belonging to fungal polyketides. They have two propane-1,2,3-tricarboxylic acid chains esterified to an aminopolyol skeleton [184]. They inhibit a ceramide synthase, the key enzyme in the biosynthetic pathway of sphingolipids, leading to serious mycotoxicoses [57,185]. Fumonisin derivatives 22–30 were isolated from F. oxysporum associated with Asparagus officinalis and Dianthus caryophyllus. They were characterized by FABMS, ES-LCMS, and NMR techniques [57,58,59,60] (Figure 2).

4.3. Jasmonates

Jasmonates are lipid-based metabolites, possessing jasmonic acid (3-oxo-2-(pent-2′-enyl)cyclopentane acetic acid) framework that are found in fungi, bacteria, and plants [186,187]. In plants, they function as growth regulators and play major roles in the defense of plants against insects and diseases [187]. In addition, hydroxylated jasmonic acids, unsaturated or saturated, and cis- or trans-configured elongated side-chain derivatives were reported from fungi. They can also form conjugates with amino acids such as isoleucine. In a study by Miersch et al., jasmonates derivatives 31–52 were purified from F. oxysporum f. sp. matthiolae using RP-18 Lichrolut, DEAE-Sephadex-A25, and 100-C18 Eurospher and characterized by GC-MS and HPLC [61] (Figure 3 and Figure 4).

4.4. Alkaloids

The reported studies revealed the isolation of diverse classes of alkaloids from F. oxysporum. Oxysporidinone (53), a novel 3,5-disubstituted N-methyl-4-hydroxy-2-pyridone was purified from F. oxysporum (CBS 330.95) culture by counter-current and SiO2 CC and characterized by UV, NMR, IR, and MS tools. It had growth inhibitory potential towards phyto-pathogenic fungi; Aspergillus niger, Botrytis cinerea, Alternaria alternata, and Venturia inequalis (MICs 10, 1, 50, and 10 µg/mL, respectively) (Table 2). It showed no observable activity towards B. subtilis, P. aeruginosa, C. albicans, and S. cervisiae (conc. 1 mg/mL) [62]. Bioassay-guided separation of F. oxysporum (N17B) extract gave three new N-methyl-4-hydroxy-2-pyridinone derivatives; 6-epi-oxysporidinone (59), dimethyl ketal of oxysporidinone (60), and N-demethylsambutoxin (61), along with (−)-oxysporidinone (54) and (−)-sambutoxin (58) that were identified by NMR and MS techniques [63] (Figure 5). Compound 54 was identical to 53 but with the opposite sign of optical rotation. Compound 59 was a 6′-hydroxy epimer of 53, however, 61 was similar to 58 with the lack of N-CH3 group. Compound 58 was isolated previously as a hemorrhagic mycotoxin from F. sambucinum [188]. Interestingly, 54 (IC50 2.0 µg/mL) had a powerful fungistatic potential towards A. fumigatus, whereas its epimer 59 (IC50 35.0 µg/mL) showed a marginal effect, compared with amphotericin B (IC50 0.91 µg/mL) in the MABA (microplate Alamar blue assay). Whilst other compounds were inactive [63]. (−)-4,6′-Anhydrooxysporidinone (57) isolated from EtOAc extract of a solid endophytic fungus F. oxysporum, had moderate anti-BS (Bacillus subtilis) activity (MIC 25.0 μg/mL) and weak anti-MRSA potential (MIC 100 μg/mL) [65]. On the other side, (−)-oxysporidinone (54), (−)-6-deoxyoxysporidinone (56), and (−)-4,6′-anhydrooxysporidinone (57) isolated from F. oxysporum EPH2RAA, harboring Ephedra fasciculata had no cytotoxic activities towards NCI-H460, MIA Pa Ca-2, MCF-7, and SF-268 [64]. Fusaric acid (63) was identified as antioomycete metabolite from F. oxysporum EF119 by MS and NMR analyses. It possessed in vivo and in vitro antioomycete potential against P. capsici (causative agent of wheat leaf rust) and P. infestans (causative agent of tomato late blight) with IC50 values < 1 µg/mL. It also completely suppressed the growth of various bacteria (IC50 values ranged from 0.2 to 12 µg/mL, Conc. < 100 µg/mL). Thus, it could be used as a biocontrol agent towards tomato late blight produced by P. infestans [66]. Moreover, 63 was identified from F. oxysporum isolated from an infected grapevine. It induced extensive necrosis formation on tobacco in the leaf-puncture assay at 0.5 mg/mL. Fusaric acid is a nonspecific toxin produced by many Fusarium species, and usually is the main phytotoxin [67]. The new fusaric acid derivatives, fusaricates A-G (65–71) and 10-hydroxy-11-chlorofusaric acid (72) purified from F. oxysporum isolated from Drepanocarpus lunatus fruits had fusaric acid linked to a polyalcohol moiety through an ester bond (Figure 6). Their structures were elucidated by NMR and MS data and the absolute configuration was established using chiral GC-MS. Only 72 had weak cytotoxicity against L5178Y (IC50 37.7 µM), compared to kahalalide F (IC50 4.3 µM).
Compounds 65, 68, 69 and 72 showed phytotoxicity towards barley leaves using cotton cotyledonary leaf bioassay almost equal to that of fusaric acid, suggesting their promising potential in organic farming. It was suggested that the existence of the C-10-hydroxyl group or C-10 and C-11 double bond led to a decrease in phytotoxicity [69]. Liu et al., postulated the biosynthetic pathway of fusaricates A-G (65–71). Isotopic 13C and 14C tracer studies revealed that C-2 to C-4 and C-7 of fusaric acid were originated from oxaloacetate, while C-5, C-6, and C-8 to C-11 were derived from three acetate units [189,190]. The nitrogen atom of pyridine ring is originated mainly from glutamine [191]. The formation of ester linkage between polyalcohols and fusaric acid could be catalyzed by lipases [192] (Scheme 2).
Nenkep et al., isolated a polycyclic quinazoline alkaloid, oxysporizoline (73), in addition to 1H-indol-3-butanamide (74) and butenolide (75) from marine-mudflat-derived F. oxysporum. Compounds 73 and 75 displayed weak antibacterial activity against MRSA (MIC 6.25 µg/mL). They also exhibited potent DPPH radical scavenging potential (IC50 10 and 12 μM, respectively) than ascorbic acid (IC50, 20 μM) [70] (Figure 6).
2-Oxo-8-azatricyclo [9.3.1.13,7]-hexadeca-1(15),3(16),4,6,11,13-hexaen-10-one (80) isolated from F. oxysporum, exhibited weak activity towards MCF-7, PC-3, and A549 and potent antimicrobial effect more than controls against various tested microorganisms with MIC values ranging from 0.8–12.5 µg/mL [73] (Figure 7). Fusarioxazin (81) was separated from F. oxysporum associated with Vicia faba roots. It displayed a significant cytotoxic effect toward HCT-116, MCF-7, and A549 cell lines (IC50s 2.1, 1.8, and 3.2 µM, respectively), in comparison to doxorubicin (IC50s 0.68, 0.54, and 0.39 µM, respectively). Additionally, it possessed antibacterial potential towards S. aureus (IZD 14.8 mm and MIC 5.3 mg/mL) and B. cereus (MIC 3.7 mg/mL and IZD 18.9 mm), in comparison to ciprofloxacin (IZDs 16.9 and 20.5 mm; MICs 3.9 and 2.3 mg/mL, respectively) [18]. Epi-trichosetin A (82), a new tetramic acid derivative, along with trichosetin (83) were separated by SiO2 and Rp-HPLC from F. oxysporum FKI-4553 broth. Compound 82 was a C-5′ epimer of 83. Compounds 82 (IC50 83 µM) and 83 (IC50 30 µM) inhibited UPP (undecaprenyl pyrophosphate) synthase activity of S. aureus. They had a broad antibacterial effect, in particular potent effect against Gram-positive bacteria, including MSSA (methicillin-sensitive S. aureus) and MRSA, where 82 appeared to be more potent than 83 in the paper disk method [74]. Kumar et al. purified vinblastine (86) and vincristine (87) from F. oxysporum isolated from Catharanthus roseus using preparative TLC and HPLC (Figure 8). They were characterized by UV-Vis, ESIMS, and NMR spectroscopy [76].

4.5. Cyclic Peptides and Depsipeptides

F. oxysporum yielded bioactive cyclic depsipeptides such as enniatins (ENs) and beauvericin (BEA, 99) (Figure 9 and Figure 10). ENs are characterized by an alternating sequence of three D-α-hydroxyisovaleric acids and three N-methyl-L-amino acids in their structure. ENs H (96), I (97), and MK1688 (98), and BEA (99) were purified from F. oxysporum KFCC-11363P submerged cultures chloroform extracts using HPLC and assessed for cytotoxicity towards A549, SK-OV-3, SK-MEL-2, and HCT15 in the SRB (sulforhodamine B). Compound 97 (EC50 0.49–0.53 µM) and MK1688 (EC50 0.45–0.63 µM) exhibited the most potent growth inhibition towards the tested cell lines that were three- to four-fold more than that of 99 and 96. On the other side, 96 and 99 exhibited powerful activity towards SK-OV-3, A549, SK-MEL-2, and HCT15 cells (EC50 1.71–2.45 µM for 96 and 1.39–1.86 µM for 99) [83]. ENs cytotoxic potential could be attributed to their ionophorous behavior, since altering the ions transport across membranes may lead to disruption of the cationic selectivity of the cell wall and induction of cell death by apoptosis accompanied by DNA fragmentation [83]. ENs A (91), A1 (92), and B1 (93) isolated from F. oxysporum N17B exhibited moderate effectiveness towards C. albicans, C. neoformans, and M. intracellulare with IC50 values ranging from 2.0 to 50.0 µg/mL in the MABA [63]. Moreover, Wang et al., reported that 99 isolated from F. oxysporum obtained from C. kanehirae bark exhibited cytotoxic potential towards A549, PC-3, and PANC-1 (IC50s 10.4, 49.5, and 47.2 μM, respectively), in comparison to cisplatin (IC50s 19.8, 26.8, and 26.2 μM, respectively) in the MTT method. It also had strong anti-MRSA and anti-BS potential (MIC 3.125 μg/mL) in the microtiter plate assay [65].
Further, 99 was obtained from the EtOAc extracts of F. oxysporum SS46 and SS50 associated with Smallanthus sonchifolius. It showed cytotoxicity against MDA-MB435, HCT-8, and SF295 (IC50s 3.17, 3.02, and 2.39 μg/mL, respectively), compared to doxorubicin (IC50 0.2, 0.04, and 0.04 μg/mL, respectively) in the MTT assay. Additionally, it had potent in vitro leishmanicidal potential (EC50 1.86 μM) towards Leishmania braziliensis, compared to geneticin (EC50 0.007 μM) [84]. Zhan et al., revealed that 99 was cytotoxic towards NCI-H460, MIA Pa Ca-2, MCF-7, and SF-268 (IC50s 1.41–2.29 µM, respectively), compared with doxorubicin (IC50 0.01–0.07 µM) [64].
Furthermore, it prohibited migration of MDA-MB-231 and PC-3M cells (conc. ranging from 3.0 to 4.0 µM and 2.0 to 2.5, respectively) in the WHA (wound healing assay). NIH ImageJ software and WHA suggested that 99 was able to inhibit PC-3M and MDA-MB-231 migration at sub-lethal concentrations. Moreover, it possessed potent antiangiogenic potential at sub-lethal concentrations, as indicated by complete inhibition of HUVEC-2 network formation at 3.0 µM below IC25 (5.0 µM) and IC50 (7.5 µM) [64]. Cyclosporine A (100) was isolated from mycelia extract of non-pathogenic F. oxysporum S6 using reversed-phase silica gel and HPLC. It prohibited the growth and suppressed sclerotia formation of the phytopathogenic fungus Sclerotinia sclerotiorum with MIC 0.1 µg/disc that made it suitable to be utilized as a bio-fungicide. Moreover, a remarkable increase in the number of surviving soybean plants was noted when F. oxysporum and S. sclerotiorum were inoculated together, in comparison to plants inoculated with S. sclerotiorum alone in the greenhouse assay. Hence, F. oxysporum could be a good biocontrol agent for S. sclerotiorum in soybean because of its metabolite 100 that was responsible for the in vitro antagonistic activity [86]. It is noteworthy to mention that some F. oxysporum strains could repress the growth of Pythium ultimum in cucumber [193] and affected S. sclerotiorum sclerotia germination [194].

4.6. Glucosylceramides

Glucosylceramides (GCs) are neutral glycosphingolipids, having glucose in 1-O-β-glycosidic linkage with a ceramide [195]. Bernardino et al., isolated and purified the GCs, 102–104 from F. oxysporum. These GCs were assessed for their potential in inducing resistance in Nicotiana tabacum cv Xanthi plants against TMV (Tobacco mosaic virus) (Figure 11). Spraying tobacco plants with GCs before virus infection reduced the incidence of necrotic lesions caused by TMV. After GCs treatment, the infected plants with the virus exhibited a reduction in HR (hypersensitive response) lesions, indicating GCs antiviral effect. The results revealed that GCs stimulated the early accumulation of H2O2 and superoxide radicals, which act as a plant immunity elicitor to combat diseases influencing the plants [87].

4.7. Quinones

Chromatographic separation of F. oxysporum f. sp. ciceris ITCC-3636 EtOAc extract afforded anhydrofusarubin (105), fusarubin (107), 8-O-methylfusarubin (108), and 3-O-methyl-8-O-methylfusarubin (109) that were elucidated by LC/ESI-MS and detailed NMR spectra (Figure 12). The EtOAc extract had strong anti-nemic activity towards Meloidogyne incognita (LC50 56.2 μg/mL) than n-BuOH fraction (LC50 97.4 μg/mL), while they were moderately active versus Rotylenchulus reniformis (LC50 134.5–189.2 μg/mL). All metabolites exhibited high anti-nemic potential towards both nematodes (LC50 ranged from 248.9 to 652.3 μg/mL). Among them, 107 showed the highest potential on both nematodes (LC50 248.9 μg/mL for M. incognita and LC50 301.6 μg/mL for R. reniformis), followed by 105 (LC50 257.6 and 285.3 μg/mL, respectively), compared to carbofuran (LC50 54.2 and 37.6 μg/mL, respectively). Whilst the methyl-substituted derivatives had moderate activity against M. incognita (LC50 ranging from 478.5 to 376.4 μg/mL) [88]. Moreover, the EtOAc extracts of F. oxysporum SS46 and SS50 isolated from Smallanthus sonchifolius yielded 105 that showed cytotoxicity against MDA-MB435, HCT-8, and SF295 (IC50 6.23, 9.85, and 6.32 μg/mL, respectively), compared to doxorubicin (IC50 0.2, 0.04, and 0.04 μg/mL, respectively) in the MTT assay [84]. Further, naphthoquinone derivatives, 106–108 and 111–115 were isolated from F. oxysporum obtained from citrus trees diseased roots. Compound 111 had strong activity towards S. aureus (MIC 4 µg/mL) and weak activity against Streptococcus pyogenes (MIC > 128 µg/mL), while 112 was moderately active against the two strains (MICs 32.0 and 64.0 µg/mL, respectively). On the other hand, 106, 108, 113, and 114 showed weak activity towards S. pyogenes in the microdilution assay [90].

4.8. Xanthone Derivatives

Bikaverin (119), intensively colored pigment was reported firstly from F. vasinfectum and F. lycopersici [85,96]. It belongs to the NRPKs (non-reducing polyketides) group that is produced by type I PKS [196,197]. By genetic engineering together with HPLC-HRMS and NMR tools, Arndt et al., identified the biosynthetic way for 119 and characterized its intermediates [198] (Scheme 3). Compounds 119 and 125 were isolated from F. oxysporum CECIS associated with Cylindropuntia echinocarpus (Figure 13). They were assessed for their cytotoxic activity towards a panel of four sentinel cancer cell lines by the MTT assay. Only 119 was cytotoxic towards NCI-H460, MIA Pa Ca-2, MCF-7, and SF-268 (IC50 0.26–0.43 µM), compared with doxorubicin (IC50 0.01–0.07 µM). It is noteworthy that 125 that lacks the C-6-OH group did not have cytotoxic activity even at concentrations of 4.0 and 2.0 µg/mL [64]. Further, 119 isolated from F. oxysporum f. sp. lycopersici as a purple-colored compound, exhibited a protective effect on oxidative stress and attenuated H2O2-induced neurotoxicity on human neuroblastoma SH-SY5Y cells. Pretreatment of neurons with 119 attenuated the H2O2 (100 µM)-induced oxidative stress through improving the cell viability, antioxidant status, mitochondrial membrane integrity, and regulation of gene expression [95]. Therefore, it could be utilized as an alternative to some of the toxic synthetic antioxidants and a preventive agent against neurodegeneration [95]. Carmen et al., reported that bikaverin-contaminated products had no negative effect on human health [199]. Kundu et al., also purified 119 from F. oxysporum f. sp. ciceris ITCC-3636 EtOAc extract that had a weak anti-nemic potential towards M. incognita (LC50 392.9 μg/mL) [88]. Additionally, Son et al., reported that 119 isolated from F. oxysporum EF119 showed antimicrobial activities against various phyto-pathogenic oomycetes and fungi. It suppressed the development of tomato late blight by 71% at conc. 300 µg/mL. Therefore, it may be used as a bio-control agent towards P. infestans-caused tomato late blight [66].

4.9. Terpenoids

Wortmannin (129) a steroidal furan, exhibited potent and selective antifungal activity toward C. albicans (IC50 0.25 µg/mL and MIC 0.78 µg/mL), compared with amphotericin B (IC50 0.35 and MIC 1.25 µg/mL) [63]. Another study revealed that 129 was a hemorrhagic factor reported from F. oxysporum (N17B) that caused different organs hemorrhage and finally death in rats and mice [98,200]. It also showed a powerful inhibitory potential of phosphatidylinositide 3-kinase [201] and had antifungal potential towards Botrytis allii [202]. Ergosta-5,8(14),22-trien-7-one,3-hydroxy-(3β,22E) (130) was characterized from F. oxysporum, which had HCV (hepatitis C virus) NS3 protease inhibitory activity (Ki 99.7 μM/L), compared to VX950 (Ki 3.5 μM/L) in the FRET (fluorescence resonance energy transfer) [99] (Figure 14).
Isoverrucarol (133), a trichothecene was isolated from F. oxysporum CJS-12, harboring corn produced toxic effects (dose 10 and 20 mg/kg/b.wt., orally) in rats, including body weakness, loss of appetite, stomach severe mucosae, and death. It also caused a definite dermatitis reaction of the epidermis and an edematic-necrotic response of the dermis [100]. FCRR (134) a new phytotoxin, having a labdane framework was purified from F. oxysporum f. sp. radicis-lycopersici (causal agent of Fusarium rot and crown rot of tomato). It (conc. 0.25 µg/mL) induced leaf necrosis for Momotaro (a cultivar of tomato, Lycopersicon esculentum Mill.) [101]. Chen et al., separated and characterized two novel compounds, fusariumins C (135) and D (136) from F. oxysporum ZZP-R1 derived from Rumex madaio. They were assigned as a meroterpene with cyclohexanone unit and a sesquiterpene ester with a conjugated triene and an unusual oxetene ring, respectively based on NMR tools and optical rotation analysis. They had a potent inhibitory effect on S. aureus (MICs 6.25 and 25 μM, respectively), however, they were weakly active towards E. coli and C. albicans in the micro-broth dilution method [102].
The sesquiterpenoid, 137 isolated from F. oxysporum LBKURCC41 obtained from Dahlia variabilis tubers showed antibacterial activity towards S. aureus and E. coli (IZD 2.1 mm) in the agar disc diffusion assay [103]. Cosmosporasides F–H (138–140), new sugar alcohol conjugated acyclic sesquiterpenes isolated from F. oxysporum SC0002, showed weak cytotoxic effect towards A549, HepG2, and HeLa (inhibition rates 13–24%) (Figure 15). They exhibited weak antibacterial potential towards S. aureus, B. cereus, E. coli, S. typhimurium, and S. dysenteriae (growth inhibition rate of 8–21%, conc. 100 µg/mL) in the Alamar blue assay. They also displayed weak inhibition of LPS-induced NO production in RAW 264.7 macrophages (9–16%, conc. 50 µM) [27].

4.10. Phenolic and Aromatic Compounds

Podophyllotoxin (151), an aryltetralin lignan was reported from F. oxysporum isolated from Juniperus recurva and quantified by HPLC, LC-MS, and LC-MS/MS [106] (Figure 16). Kılıç et al., reported the isolation of 153 from F. oxysporum YP9B that displayed potent cytotoxic potential towards MCF-7, PC-3, and A549 (IC50 15.01, 19.13, and 17.06 µM, respectively), compared to doxorubicin (IC50 0.053, 0.09, 17.75 µM, respectively). It showed antiviral potential towards the HSV type-1 virus that lysed VERO cells. It produced a partial increase in VERO cell viability (conc. 0.312 µM). Moreover, it had a powerful antibacterial potential (MICs 0.47–1.8 µg/mL) towards B. cereus, S. mutans, S. aureus, E. faecalis, and M. smegmatis [73].

4.11. Pyran and Furan Derivatives

Chlamydosporol (158) a pyran lactone derivative was isolated from marine-mudflat-derived F. oxysporum and assessed for its antibacterial potential towards MRSA and MDRSA. It displayed weak antibacterial activity against MRSA and MDRSA (MIC 31.5 µg/mL) [70]. The co-culture of F. oxysporum R1 and A. fumigatus D afforded neovasinin (160) and neovasifuranone B (163) that had a weak antimicrobial activity towards E. coli, S. aureus, and C. albicans (MICs ≥ 25 μM) [72] (Figure 17).

4.12. Aliphatic Acids

Mixtures of acid esters: 165–167, 168 and 169, and 170–172 were identified from F. oxysporum YP9B by NMR, UV, FT-IR, and GC-FID- and LC-QTOF-MS [73]. Only 170–172 mixture showed potent cytotoxic activity on MCF-7, PC-3, and A549 (IC50 7.75, 17.75, and 7.51 µM, respectively), compared to doxorubicin (IC50 0.053, 0.09, and 17.75 µM, respectively), where it was about two folds more active than doxorubicin on A549. Only the mixture of 168 and 169 caused a partial cell viability increase (conc. 1.25 µM) in the antiviral assay towards HSV-I. Moreover, they exhibited strong to weak antimicrobial potential towards various tested microorganisms. On the other hand, the mixture of 170–172 showed potent activity only against S. aureus ATCC25923, E. faecalis ATCC29212, S. mutans RSKK07038, and B. cereus 702 Roma (MIC ranging from 2.1 to 4.3 µg/mL) [73]. Yu et al., purified compounds 173–175 from F. oxysporum R1 and A. fumigatus D co-culture, which displayed weak antimicrobial activity (MICs ≥ 25 μM) towards E. coli, S. aureus, and C. albicans [72] (Figure 18).

4.13. Volatile Organic Compounds

GCMS analysis of the VOCs (volatile organic compounds) of F. oxysporum isolate 21 obtained from coffee plant rhizosphere, Meloidogyne exigua eggs and egg masses revealed the existence of 38 VOCs, five of them were above 1% (dioctyl disulfide, 1-(2-hydroxyethoxy) tridecane or 2-propyldecan-1-ol, 4-methyl-2,6-di-tert-butylphenol, caryophyllene, and acoradiene). VOCs from F. oxysporum displayed nematicidal potential towards M. incognita, thus it could be useful for the development of bio-control agent for Meloidogyne spp. in coffee fields [203].
do Nascimento et al., reported that GCMS of n-hexane extract of F. oxysporum SS50 isolated from Smallanthus sonchifolius revealed twelve compounds; pentadecane, (2E,4E)-decadienal, hexadecane, octadecane, heptadecane, bis(2-methylpropyl) ester, 1,2-benzenedicarboxylic acid, methyl hexadecanoate or methyl palmitate, (9Z,12Z)-octadecadienoic acid methyl ester, clionasterol, dehydroergosterol, (9Z)-octadecenoic acid methyl ester, and stigmast-4-en-3-one, where fatty acid methyl esters and alkanes were predominated (4.70% (9Z)-octadecenoic acid methyl ester, 9.73% methyl hexadecanoate, and 54.45% (9Z,12Z)-octadecadienoic acid methyl ester). The n-hexane extract possessed cytotoxic activity towards HCT-8, MDA-MB435, and SF295 (% growth inhibition ranging from 83.78 to 97.72%, conc. 50 μg/mL) in the MTT assay. This could be attributed to the mixture of three methyl esters [84].

5. Conclusions and Future Research Directions

Currently, more focus has been directed to fungi as they are a wealthy platform for the biosynthesis of a huge number of structural diverse metabolites. F. oxysporum is a species with great physiological and morphological variations and its wide-ranging existence in ecological activities worldwide indicates its profoundly diversified and significant role in nature. It can produce various bio-metabolites that may directly and indirectly be utilized as therapeutic agents for various health problems. In this work, 180 metabolites were reported from F. oxysporum in the period from 1967 to 2021. Alkaloids quinones, and jasmonates, and anthranilate derivatives represented the major metabolites that were isolated from this fungus (Figure 19).
Although, this big number of reported metabolites, few of them are evaluated for their bioactivities. The assessed activities of these metabolites were antimicrobial, cytotoxicity, nematicidal, antiviral, leishmanicidal, antiviral, and antioxidant. Additionally, there is a lack of pharmacological studies that focus on exploring the possible mechanisms of the active metabolites. In addition, the untested metabolites should be further explored for their possible bioactivities. Co-cultivation experiments should be employed to elicit the production of these metabolites. The discovery of the underlying biosynthetic pathways of these bio-metabolites is needed, which would allow the rational engineering or refactoring of these pathways for industrial purposes. Further, research for identifying the responsible biosynthetic genes for these metabolites may open the opportunity to explore the genetic potential of F. oxysporum for discovering novel metabolites by metabolic engineering that could result in more affordable and novel pharmaceutics and food additives. Moreover, studies on the structure-activity relationships and/or derivatization of these fungus metabolites should be carried out.
Although, the reported data revealed that F. oxysporum is widely employed for the synthesis of different types of metal nanoparticles that could have various biotechnological, agronomical, pharmaceutical, industrial, and medicinal applications. Many of these biosynthesized NPs possessed favorable antimicrobial potential, especially towards MDR microbes that can be potential alternatives to antibiotics. Further, it was found that the combination of NPs synthesized using F. oxysporum with antibiotics produced additive and synergic effects that could represent a new strategy for treating some antibiotics resistant strains and lower the doses of the used antibiotics. F. oxysporum might have vast commercial implications in low-cost, room-temperature, ecofriendly syntheses of technologically significant oxide nanomaterials from naturally available potentially cheap raw materials. However, the NPs synthesized from F. oxysporum are limited to metals and fewer metal oxides and sulfides. Therefore, future research should focus on developing protocols for implementing the biosynthesis of NPs of other metals, metal oxides, nitrides, and carbides. Research on the toxic effect of these NPs, as well as their effects on animals and human health and accumulation in the environment, is needed.
Additionally, in-vivo studies and clinical trials are needed to elaborate the exact mechanism responsible for their observed bioactivities. There is also a need for evaluating these NPs for their effectiveness towards various diseases, which can open in the future a new avenue in the biomedical field. More research is required for optimizing various reaction conditions to achieve better control over the shape, size, stability, and monodispersity of these NPs. F. oxysporum is considered as an efficient enzyme producer. Its enzymes have attracted great interest because of their possible applications in diverse biotechnological and industrial fields such as pharmaceutical, cosmetic, and food industries, organic synthesis, bioremediation, and detoxification of environmental pollutants, delignification, denitrification, or biofuel production. Additionally, they are involved in eco-friendly bioconversion processes of various substrates to highly valuable products that could be preferred more over the chemical synthesis. Research that focuses on engineering enzymes in such a way for maximum stability and activity under appropriate conditions is desirable. Recombinant DNA technology and engineering of proteins are required to improve the industrial production of these enzymes. Additionally, some F. oxysporum strains can be utilized as bio-control agents because of their ability to prohibit the growth of several fungal plant pathogens.

Author Contributions

Conceptualization, S.R.M.I. and G.A.M.; Resources, G.A.M., S.R.M.I., and S.G.A.M.; Discussion of the contents, A.S. and B.G.E., Writing—Original Draft Preparation, S.R.M.I., G.A.M., and S.G.A.M., Writing—Review and Editing, G.A.M., S.R.M.I., A.S. and B.G.E. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

A549Human non-small-cell lung cancer cell line
AgNPsSilver nanoparticles; AGS: Gastric adenocarcinoma
APaseβ-L-Arabinopyranosidase
BGLβ-Glucosidases
Bi2S3Bismuth sulphide
C26Murine colon carcinoma
CBPConsolidated bioprocessing
CdSeCadmium/selenium
CLEAsCross-linked enzyme aggregates
CLSMConfocal laser scanning microscopic
DHAPDihydroxyactetone-3-phosphate
DHBA2,3-Dihydroxybenzoic acid
DPPH2,2-Diphenyl-1-picrylhydrazyl
EC50Concentration required inhibiting cell growth in vitro by 50%
ESBLExtended-spectrum beta-lactamase
FAODFructosyl amino acid oxidase
FLCFluconazole
FLOFructosyl lysine oxidase
FRETFluorescence resonance energy transfer
FUCα-L-Fucosidase
GAPGlyceraldehyde-3-phosphate
GH-11Glycosyl hydrolase family 11
GNPsGold nanoparticles
GPaseα-D-Galactopyranosidase
HaCaTHuman immortalized keratinocyte cells
HCT116Human colorectal adenocarcinoma
HCT15Human colorectal cancer cell line
HCT8Human colon tumor cell lines
HeLaHuman cervix carcinoma cell line
HepG2Human liver cancer cell line
HUVEC-2Human umbilical vascular endothelial cells
IC50Concentration causing 50% growth inhibition
ILIonic liquid
IZDInhibition zone diameter
L5178YMouse lymphoma cell line
LCLethal concentration
LDHLactate dehydrogenase release assay
LMSLaccase mediator system
LOXLipoxygenase
MABAMicroplate Alamar blue assay
MBMethylene blue
MCF-7Breast cancer cell line
MDA-MB-231Metastatic breast cancer cell line
MDA-MB435Human melanoma tumor cell lines
MDRMultidrug-resistant
MIA Pa Ca-2Pancreati cancer cell line
MICMinimum inhibitory concentration
MRSAMethicillin-resistant Staphylococcus aureus
MRSAMethicillin-resistant S. aureus
MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)
N2ODinitrogenoxide
NCI-H460Non-small-cell lung
NONitrogen monoxide
NORNitric oxide reductase
NPsNanoparticles
OMWOlive Mill Waste
PANC-1Human Pancreatic cancer cell line
PC-3Human prostate carcinoma cell line
PC-3MMetastatic prostate cancer cell line
PDAPotato dextrose agar
PETPolyethylene terephthalate
PLBPhospholipase B
PNP-α-D-GalpPara-nitrophenyl α-D-galactopyranoside
PNP-β-L-ArapPara-nitrophenyl α-l-arabinopyranoside
SF-268Central nervous system glioma
SF295Human brain tumor cell lines
SK-MEL-2Skin cancer cell line
SK-OV-3Ovarian cancer cell line
SRBSulforhodamine B
TAGTriacylglycerols
TPITriosephosphate isomerase
UPPUndecaprenyl pyrophosphate
VOCsVolatile organic compounds
WHAWound healing assay

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Scheme 1. Possible biosynthetic pathway for the formation of anthranilic acid derivatives [56,182,183].
Scheme 1. Possible biosynthetic pathway for the formation of anthranilic acid derivatives [56,182,183].
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Figure 1. Structures of anthranilic acid derivatives (1–21) isolated from F. oxysporum.
Figure 1. Structures of anthranilic acid derivatives (1–21) isolated from F. oxysporum.
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Figure 2. Structures of fumonisins 22–30 isolated from F. oxysporum.
Figure 2. Structures of fumonisins 22–30 isolated from F. oxysporum.
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Figure 3. Structures of jasmonates derivatives (31–42) isolated from F. oxysporum.
Figure 3. Structures of jasmonates derivatives (31–42) isolated from F. oxysporum.
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Figure 4. Structures of jasmonates derivatives (43–52) isolated from F. oxysporum.
Figure 4. Structures of jasmonates derivatives (43–52) isolated from F. oxysporum.
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Figure 5. Structures of pyridinone alkaloids (53–61) isolated from F. oxysporum.
Figure 5. Structures of pyridinone alkaloids (53–61) isolated from F. oxysporum.
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Scheme 2. Possible biosynthetic pathway of fusaricates A-G (65–71) [69].
Scheme 2. Possible biosynthetic pathway of fusaricates A-G (65–71) [69].
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Figure 6. Structures of alkaloids (62–75) isolated from F. oxysporum.
Figure 6. Structures of alkaloids (62–75) isolated from F. oxysporum.
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Figure 7. Structures of alkaloids (76–85) isolated from F. oxysporum.
Figure 7. Structures of alkaloids (76–85) isolated from F. oxysporum.
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Figure 8. Structures of alkaloids (86–90) isolated from F. oxysporum.
Figure 8. Structures of alkaloids (86–90) isolated from F. oxysporum.
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Figure 9. Structures of cyclic depsipeptides (91–96) isolated from F. oxysporum.
Figure 9. Structures of cyclic depsipeptides (91–96) isolated from F. oxysporum.
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Figure 10. Structures of cyclic depsipeptides (97–99) and cyclic peptide (100) isolated from F. oxysporum.
Figure 10. Structures of cyclic depsipeptides (97–99) and cyclic peptide (100) isolated from F. oxysporum.
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Figure 11. Structures of glucosylceramides (101–104) isolated from F. oxysporum.
Figure 11. Structures of glucosylceramides (101–104) isolated from F. oxysporum.
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Figure 12. Structures of naphthoquinone (105–115) and anthraquinone (116) derivatives isolated from F. oxysporum.
Figure 12. Structures of naphthoquinone (105–115) and anthraquinone (116) derivatives isolated from F. oxysporum.
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Scheme 3. Putative biosynthetic pathway of 119 and its intermediates. The bold arrows represent the preferred pathway and dashed lines represented other possible reaction steps [196,197,198].
Scheme 3. Putative biosynthetic pathway of 119 and its intermediates. The bold arrows represent the preferred pathway and dashed lines represented other possible reaction steps [196,197,198].
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Figure 13. Structures of xanthone derivatives (117–125) isolated from F. oxysporum.
Figure 13. Structures of xanthone derivatives (117–125) isolated from F. oxysporum.
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Figure 14. Structures of sterols (126–132) isolated from F. oxysporum.
Figure 14. Structures of sterols (126–132) isolated from F. oxysporum.
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Figure 15. Structures of terpenoids (133–141) isolated from F. oxysporum.
Figure 15. Structures of terpenoids (133–141) isolated from F. oxysporum.
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Figure 16. Structures of terpenoids (142–145), flavonoids (146 and 147), depsidones (148–150), lignan (151), and phenolic compound (152).
Figure 16. Structures of terpenoids (142–145), flavonoids (146 and 147), depsidones (148–150), lignan (151), and phenolic compound (152).
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Figure 17. Structures of aromatic compounds (153–157), pyran (158–160) and furan (161–164) derivatives, and aliphatic acids (165–172) isolated from F. oxysporum.
Figure 17. Structures of aromatic compounds (153–157), pyran (158–160) and furan (161–164) derivatives, and aliphatic acids (165–172) isolated from F. oxysporum.
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Figure 18. Structures of fatty acids (173–175) and sugar derivatives (176–180) isolated from F. oxysporum.
Figure 18. Structures of fatty acids (173–175) and sugar derivatives (176–180) isolated from F. oxysporum.
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Figure 19. Different classes of metabolites reported from F. oxysporum.
Figure 19. Different classes of metabolites reported from F. oxysporum.
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Table
Table 1. List of compounds isolated from F. oxysporum (chemical class, molecular weight and formulae, fungal source, host, and place).
Table 1. List of compounds isolated from F. oxysporum (chemical class, molecular weight and formulae, fungal source, host, and place).
Compound NameMol. Wt.Mol. FormulaFungal SourceHost (Part, Family)PlaceRef.
Anthranilic Acid Derivatives
Dianthramide (1)283C16H13NO4F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae) 		The Netherlands[56]
Dianthramide B (2)241C14H11NO3F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Hydroxydianthramide B (3)257C14H11NO4F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Hydroxydianthramide M (4)303C15H15NO6F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Hydroxydianthramide S (5)273C14H11NO5F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Hydroxydianthramide R (6)289C14H11NO6F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Methoxydianthramide M (7)317C16H15NO6F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Methoxydianthramide B (8)271C15H13NO4F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Methoxydianthramide S (9)287C15H13NO5F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Methoxydianthramide R (10)303C15H13NO6F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Methoxydianthramide A (11)301C16H15NO5F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Hydroxydianthramide S ethyl ester (12)301C16H15NO5F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Hydroxydianthramide S methyl ester (13)287C15H13NO5F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Methoxydianthramide A methyl ester (14)315C15H13NO5F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Hydroxyanilide B (15)213C13H11NO2F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Hydroxyanilide S (16)229C13H11NO3F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Hydroxyanilide R (17)245C15H13NO5F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Dianthalexin B (18)223C14H9NO2F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Hydroxydianthalexin B (19) =
Dianthalexin 		239C14H9NO3F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Hydroxydianthalexin S (20)255C14H9NO4F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Methoxydianthalexin S (21)269C15H11NO4F. oxysporum f. sp. dianthiDianthus caryophyllus,
stem (Caryophyllaceae)		The Netherlands[56]
Fumonisins
Fumonisin B1 (22)721C34H59NO15F. oxysporumAsparagus officinalis
(Asparagaceae)		Western Poland[57]
Hydroxylated fumonisin C1 (23)723C33H57NO16F. oxysporum CARDianthus caryophyllus
(Caryophyllaceae)		Taejon, Korea[58,59]
Fumonisin C1 (24)707C33H57NO15F. oxysporum CARDianthus caryophyllus
(Caryophyllaceae)		Taejon, Korea[58,59]
Fumonisin C3 (25)691C33H57NO14F. oxysporum CARDianthus caryophyllus
(Caryophyllaceae)		Taejon, Korea[58,59]
Fumonisin C4 (26)675C33H57NO13F. oxysporum CARDianthus caryophyllus
(Caryophyllaceae)		Taejon, Korea[58,59]
Iso-Fumonisin C1 (27)707C33H57NO15F. oxysporum KCTC 16654Asparagus officinalis
(Asparagaceae)		Taejon, Korea[60]
N-Acetylated OH-fumonisin C1 (28)765C35H59NO17F. oxysporum KCTC 16654Asparagus officinalis
(Asparagaceae)		Taejon, Korea[60]
N-Acetylated fumonisin C1 (29)749C35H59NO16F. oxysporum KCTC 16654Asparagus officinalis
(Asparagaceae)		Taejon, Korea[60]
N-Acetylated iso-fumonisin C1 (30)749C35H59NO16F. oxysporum KCTC 16654Asparagus officinalis
(Asparagaceae)		Taejon, Korea[60]
Jasmonates derivatives
(−)-Jasmonic acid (31)210C12H18O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
(+)-7-Iso-jasmonic acid (32)210C12H18O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
(1S,2R)-3-Oxo-2-(2Z-pentenyl)
cyclopentane-1-butyric acid (33)		238C14H22O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
(1S,2S)-3-(1S,2S)-3-Oxo-2-(2Z-pentenyl)cyclopentane-1-butyric acid (34)238C14H22O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
(1S,2R)-3-Oxo-2-(2Z-pentenyl)
cyclopentane-1-hexanoic acid (35)		266C16H26O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
(1S,2S)-3-Oxo-2-(2Z-pentenyl)
cyclopentane-1-hexanoic acid (36)		266C16H26O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
(1S,2R)-3-Oxo-2-(2Z-pentenyl)
cyclopentane-1-octanoic acid (37)		294C18H30O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
(1S,2S)-3-Oxo-2-(2Z-pentenyl)
cyclopentane-1-octanoic acid (38)		294C18H30O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
9,10-Dihydrojasmonic acid (39)212C12H20O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
9,10-Dihydro-7-iso-jasmonic acid (40)212C12H20O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
(1S,2R)-3-Oxo-2-pentylcyclopentane-1-butyric acid (41)240C14H24O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
(1S,2S)-3-Oxo-2-pentylcyclopentane-1-butyric acid (42)240C14H24O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
(1S,2R)-3-Oxo-2-pentylcyclopentane-1-hexanoic acid (43)268C16H28O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
(1S,2S)-3-Oxo-2-pentylcyclopentane-1-hexanoic acid (44)268C16H28O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
(1S,2R)-3-Oxo-2-pentylcyclopentane-1-octanoic acid (45)296C18H32O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
(1S,2S)-3-Oxo-2-pentylcyclopentane-1-octanoic acid (46)296C18H32O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
7-Iso-cucurbic acid (47)212C12H20O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
Cucurbic acid (48)212C12H20O3F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
N-(−)-Jasmonoyl-(S)-isoleucine (49)323C18H29NO4F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
N-(+)-7-Iso-jasmonoyl-(S)-isoleucine (50)323C18H29NO4F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
N-(9,10-Dihydrojasmonoyl)-(S)-isoleucine (51)325C18H31NO4F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
N-(9,10-Dihydro-7-iso-jasmonoyl)-(S)-isoleucine (52)325C18H31NO4F. oxysporum f. sp. matthiolaeCulturedThe Netherlands[61]
Alkaloids
Oxysporidinone (53)489C28H43NO6F. oxysporum CBS 330.95PlantSweden[62]
(−)-Oxysporidinone (54)489C28H43NO6F. oxysporum N17BCulturedMississippi, USA[63]
F. oxysporum EPH2RAAEphedra fasciculate, root (Ephedraceae)Sonoran Desert, USA[64]
(−)-4’-Hydroxyl oxysporidinone (55)491C28H45NO6F. oxysporumCinnamomum kanehirae, bark (Lauraceae)Jiaoban Mountain, Taiwan. China[65]
(−)-6-Deoxyoxysporidinone (56)473C28H43NO5F. oxysporum EPH2RAAEphedra fasciculate, root (Ephedraceae)Sonoran Desert, USA[64]
(−)-4,6’-Anhydrooxysporidinone (57)471C28H41NO5F. oxysporum EPH2RAAEphedra fasciculate, root (Ephedraceae)Sonoran Desert, USA[64]
F. oxysporumCinnamomum kanehirae, bark (Lauraceae)Jiaoban Mountain, Taiwan. China[65]
(−)-Sambutoxin (58)453C28H39NO5F. oxysporum N17BCulturedMississippi, USA[63]
6-Epi-oxysporidinone (59)489C28H43NO6F. oxysporum N17BCulturedMississippi, USA[63]
Dimethyl ketal of oxysporidinone (60)535C30H49NO7F. oxysporum N17BCulturedMississippi, USA[63]
N-Demethylsambutoxin (61)439C27H37NO4F. oxysporum N17BCulturedMississippi, USA[63]
2-Phenylpropionyl-2-piperidinone-3-(R)-yl ester (62)247C14H17NO3F. oxysporumCinnamomum kanehirae, bark (Lauraceae)Jiaoban Mountain, Taiwan. China[65]
Fusaric acid (63)179C10H13NO2F. oxysporum EF119Capsicum annuum, root (Solanaceae)Taejon, Korea[66]
F. oxysporumVitis vinifera, plant (Vitaceae)Firenze, Italy[67]
9,10-Dehydrofusaric acid (64)177C10H11NO2F. oxysporum f. sp. pisi, F42 and F69CulturedUSA[68]
Fusaricate A (65)253C13H19NO4F. oxysporumDrepanocarpus lunatus, fruit (Fabaceae) Douala, Cameroon[69]
Fusaricate B (66)269C13H19NO5F. oxysporumDrepanocarpus lunatus, fruit (Fabaceae)Douala, Cameroon[69]
Fusaricate C (67)283C14H21NO5F. oxysporumDrepanocarpus lunatus, fruit (Fabaceae)Douala, Cameroon[69]
Fusaricate D (68)313C15H23NO6F. oxysporumDrepanocarpus lunatus, fruit (Fabaceae)Douala, Cameroon[69]
Fusaricate E (69)313C15H23NO6F. oxysporumDrepanocarpus lunatus, fruit (Fabaceae)Douala, Cameroon[69]
Fusaricate F (70)311C15H21NO6F. oxysporumDrepanocarpus lunatus, fruit (Fabaceae)Douala, Cameroon[69]
Fusaricate G (71)311C15H21NO6F. oxysporumDrepanocarpus lunatus, fruit (Fabaceae)Douala, Cameroon[69]
10-Hydroxy-11-chlorofusaric acid (72)215C9H10ClNO3F. oxysporumDrepanocarpus lunatus, fruit (Fabaceae)Douala, Cameroon[69]
Oxysporizoline (73)446C28H22N4O2F. oxysporumMarine mudflat Suncheon Bay, Korea[70]
1H-Indol-3-butanamide (74)202C12H14N2OF. oxysporumMarine mudflat Suncheon Bay, Korea[70]
Butenolide (75)141C6H7NO3F. oxysporumMarine mudflat Suncheon Bay, Korea[70]
Cyclo-(L-prolyl-L-glycine) (76)154C7H10N2O2F. oxysporum UDLAP 21-92Cultured Mexico[71]
Cyclo-(L-prolyl-L-valine) (77)196C10H16N2O2F. oxysporum UDLAP 21-92Cultured Mexico[71]
Cyclo-(L-leucyl-L-proline) (78)210C11H18N2O2F. oxysporum UDLAP 21-92Cultured Mexico[71]
(S,E)-Methyl-2-(2,4-dimethylhex-2-enamido)acetate (79)213C11H19NO3F. oxysporum R1 and
Aspergillus fumigatus
D co-culture		Rumex madaio
(Polygonaceae)
Edgeworthia chrysantha (Thymelaeaceae)		China[72]
2-Oxo-8-azatricyclo [9.3.1.13,7]-hexadeca
-1(15),3(16),4,6,11,13-hexaen-10-one (80)		225C14H11NO2F. oxysporum YP9BSolanum lycopersicum, root, (Solanaceae)Pazar-Rize, Turkey[73]
Fusarioxazin (81)337C20H19NO4F. oxysporumVicia faba, root,
(Fabaceae)		Assiut, Egypt[18]
Epi-trichosetin (82)359C21H29NO4F. oxysporum FKI-4553CulturedJapan[74]
Trichosetin (83)359C21H29NO4F. oxysporum FKI-4553CulturedJapan[74]
N-(2-Phenylethyl)acetamide (84)177C11H15NOF. oxysporum R1
and Aspergillus fumigatus D co-culture		Rumex madaio
(Polygonaceae)
Edgeworthia chrysantha (Thymelaeaceae)		China[72]
Siderophore (85)344C16H12N2O7F. oxysporumMusa acuminata
(Musaceae)		Colombo, Sri Lanka[75]
Vinblastine (86)810C46H58N4O9F. oxysporumCatharanthus roseus,
leaf (Apocynaceae)		India[76]
Vincristine (87)824C46H58N4O10F. oxysporumCatharanthus roseus,
leaf (Apocynaceae)		India[76]
Taxol (88)853C47H51NO14F. oxysporumRhizophora annamalayana, leaf (Rhizophoraceae)Vellar Estuary, Tamil Nadu[77]
Flavin adenine dinucleotide (89)785C27H33N9O15P2F. oxysporumCulturedUSA[78]
Flavin adenine dinucleotide-N(5)-Nitrobutane (90)888C31H42N10O17P2F. oxysporum ATCC 695CulturedUSA[78]
F. oxysporum ATCC 695CulturedUSA[79]
Cyclic depsipeptides
Enniatin A (91)681C36H63N3O9F. oxysporum f. sp. pisiCulturedGermany[80]
Enniatin A1 (92)667C35H61N3O9F. oxysporum f. sp. melonis ITEM 3464Cucumis melo
(Cucurbitaceae)		Rome, Italy[81]
F. oxysporum N17BCulturedMississippi, USA[63]
Enniatin B (93)639C33H57N3O9F. oxysporum f. sp. pisiCulturedGermany[80]
F. oxysporum f. sp. melonis ITEM 3464Cucumis melo
(Cucurbitaceae)		Rome, Italy[81]
Enniatin B1 (94)653C34H59N3O9F. oxysporum f. sp. melonis ITEM 3464Cucumis melo
(Cucurbitaceae)		Rome, Italy[81]
F. oxysporum N17BCulturedMississippi, USA[63]
Enniatin C (95)681C36H63N3O9F. oxysporum f. sp. pisiCulturedGermany[80]
Enniatin H (96) 653C34H59N3O9F. oxysporum FB1501
(KFCC 11363P)		SoilKorea[82]
F. oxysporum KFCC 11363PSoilKorea[83]
Enniatin I (97)667C35H61N3O9F. oxysporum FB1501
(KFCC 11363P)		SoilKorea[82]
F. oxysporum KFCC 11363PSoilKorea[83]
Enniatin MK 1688 (98)681C36H63N3O9F. oxysporum FB1501
(KFCC 11363P)		SoilKorea[82]
F. oxysporum KFCC 11363PSoilKorea[83]
Beauvericin (99)783C45H57N3O9F. oxysporum f. sp. melonis ITEM 3464Cucumis melo
(Cucurbitaceae)		Rome, Italy[81]
F. oxysporum FB1501
(KFCC 11363P)		Soil Korea[82]
F. oxysporum EPH2RAAEphedra fasciculate, root (Ephedraceae)Sonoran Desert, USA[64]
F. oxysporum KFCC 11363PSoil Korea[83]
F. oxysporumCinnamomum kanehirae, bark (Lauraceae)Jiaoban Mountain,
Taiwan. China		[65]
F. oxysporum SS46 and SS50Smallanthus sonchifolius, root (Asteraceae)Brazil[84]
F. oxysporumDrepanocarpus lunatus, fruit (Fabaceae)Douala, Cameroon[69]
F. oxysporum LCP 531SoilFrance[85]
Cyclic peptides
Cyclosporine A (100)1201C62H111N11O12F. oxysporum S6Soil of soybean fieldSalto, Buenos Aires, Argentina[86]
Glucosylceramides
Fusaruside (101)751C43H77NO9F. oxysporumCinnamomum kanehirae, bark (Lauraceae)Jiaoban Mountain,
Taiwan, China		[65]
(2S,2′R,3R,3′E,4E,8E)-1-O-D-Glucopyranosyl-2-N-(2′-hydroxy-3′-octadecenoyl)-3-hydroxy-9-methyl-4,8-
sphingadienine (102)		753C43H79NO9F. oxysporumCinnamomum kanehirae, bark (Lauraceae)Jiaoban Mountain,
Taiwan, China		[65]
F. oxysporum IOC 4247CulturedBrazil[87]
N-2′-Hydroxyoctadecanoic-1-β-D-glucopyranosyl-9-methy-l-4-hydroxy-4,8- sphingadienine (103)771C43H81NO10F. oxysporum IOC 4247CulturedBrazil[87]
N-2′-Hydroxyeicosanoyl-
1-β-D-glucopyranosyl-9-methyl-4,8-
sphingadienine (104)		783C45H85NO9F. oxysporum IOC 4247CulturedBrazil[87]
Naphthoquinone derivatives
Anhydrofusarubin (105)288C15H12O6F. oxysporum SS46 and SS50Smallanthus sonchifolius, root (Asteraceae)Brazil[84]
F. oxysporum f. sp. ciceris
ITCC 3636		CulturedIndia[88]
8-O-Methylbostrycoidin (106)299C16H13NO5F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[89]
F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[90]
Fusarubin (107)306C15H14O7F. oxysporum f. sp. ciceris
ITCC 3636		CulturedIndia[88]
9-O-Methylfusarubin (108) = 8-O-Methylfusarubin320C16H16O7F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[89]
F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[90]
F. oxysporum f. sp. ciceris
ITCC 3636		CulturedIndia[88]
3-O-Methyl-9-O-methylfusarubin (109) = 3-O-Methyl-8-O-methylfusarubin334C17H18O7F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[89]
F. oxysporum f. sp. ciceris
ITCC 3636		CulturedIndia[88]
9-O-Methylanhydrofusarubin (110)302C16H14O6F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[89]
8-O-Methyljavanicin (111)304C16H16O6F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[89]
F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[90]
8-O-Methylsolaniol (112)306C16H18O6F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[89]
F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[90]
8-O-Methyl-2-hydroxyjavanicin (113)306C15H14O7F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[89]
F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[90]
Nectriafurone (114)304C15H12O7F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[91]
F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[90]
Nectriafurone-8-methy ether (115)318C16H14O7F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[91]
Anthraquinone derivatives
Rhodolamprometrin (116)314C16H10O7F. oxysporumCECISEphedra fasciculate, root (Ephedraceae)Sonoran Desert, USA[64]
2-Acetyl-3,8-dihydroxy-6-methoxy-anthraquinone (117)312C17H12O6F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[92]
2-(1-Hydroxyethyl)-3,8-dihydroxy-6-methoxy-anthraquinone (118)314C17H14O6F. oxysporumCitrus sinensis, root
(Rutaceae)		Florida, USA[92]
Xanthone derivatives
Bikaverin (119) 382C20H14O8F. oxysporumCulturedUSA[93]
F. oxysporum CECISEphedra fasciculate, root (Ephedraceae)Sonoran Desert, USA[64]
F. oxysporumCultured USA[94]
F. oxysporum EF119Capsicum annuum, root (Solanaceae)Taejon, Korea[66]
F. oxysporum f. sp. lycopersiciRhizosphere soil of
tomato plant		India[95]
F. oxysporum f. sp. ciceris
ITCC 3636		CulturedIndia[88]
F. oxysporum LCP 531SoilFrance[85,96]
Norbikaverin (120) 352C19H12O7F. oxysporum LCP 531SoilFrance[85,96]
Oxo-Pre-bikaverin (121)338C18H10O7F. oxysporum LCP 531SoilFrance[85]
Me-oxo-pre-bikaverin (122)352C19H12O7F. oxysporum LCP 531SoilFrance[85]
Dinor-bikaverin (123)354C18H10O8F. oxysporum LCP 531SoilFrance[85]
Pre-bikaverin (124)324C18H12O6F. oxysporum LCP 531SoilFrance[85]
6-Deoxybikaverin (125)366C20H14O7F. oxysporumCECISEphedra fasciculate, root (Ephedraceae)Sonoran Desert, USA[64]
Terpenoids
Ergosterol (126)396C28H44OFusarium oxysporum
CM 192679		CulturedKew, England[97]
F. oxysporum LCP 531SoilFrance[85]
Ergosterol peroxide (127)428C28H44O3F. oxysporum CM 192679CulturedKew, England[97]
Cerevisterol (128)430C28H46O3F. oxysporum CM 192679CulturedKew, England[97]
F. oxysporumCinnamomum kanehirae, bark (Lauraceae)Jiaoban Mountain, Taiwan, China[65]
F. oxysporumVicia faba, root (Fabaceae)Assiut, Egypt[18]
Wortmannin (129)428C23H24O8F. oxysporum N17BSoil sampleGrassy field near the city of
Lakselv in the Arctic
region of Norway		[98]
F. oxysporum N17BCulturedMississippi, USA[63]
H1-A = Ergosta-5,8 (14),22-trien-7-one, 3-hydroxy-(3β, 22E) (130)410C28H42O2F. oxysporumSIPI-4004Cultured China[99]
(22E,24R)-Stigmasta-5,7,22-trien-3-β-ol (131)410C29H46OF. oxysporumVicia faba, root (Fabaceae)Assiut, Egypt[18]
Stigmasta-4,6,8(14),22-tetraen-3-one (132)406C29H42OF. oxysporumVicia faba, root (Fabaceae)Assiut, Egypt[18]
Isoverrucarol (133)266C15H22O4Fusarium oxysporum CJS-12Zea mays (Poaceae)Jeongsun District, Kangwon, South Korea[100]
FCRR-toxin (134)346C20H26O5F. oxysporum f.
sp. radicis-lycopersici		Lycopersicon esculentum, root (Solanaceae)Japan[101]
Fusariumin C (135)332C21H32O3F. oxysporum ZZP-R1Rumex madaio
(Polygonaceae)		Putuo Island, Zhoushan, China[102]
Fusariumin D (136)264C16H24O3F. oxysporum ZZP-R1Rumex madaio
(Polygonaceae)		Putuo Island, Zhoushan, China[102]
(1R,2S,3R)-3-((S)-2-Hydroxy-6-methylhept-5-en-2-yl)-1,2-
dimethylcyclopentanol (137)		240C15H28O2F. oxysporum LBKURCC41Dahlia variabilis,
tuber (Asteraceae)		Padang Luar,
West Sumatra, Indonesia		[103]
Cosmosporaside F (138)536C26H48O11F. oxysporum SC0002Soil Dinghu Mountain Biosphere Reserve, Guangdong, China[27]
Cosmosporaside G (139)532C27H48O10F. oxysporum SC0002Soil Dinghu Mountain Biosphere Reserve, Guangdong, China[27]
Cosmosporaside H (140)546C28H50O10F. oxysporum SC0002Soil Dinghu Mountain Biosphere Reserve, Guangdong, China[27]
Ginkgolide B (141)424C20H24O10F. oxysporumSYP0056Ginkgo biloba, root
bark (Ginkgoaceae)		Forest site, Changbai
Mountain, China		[104]
Trichothecenes T-2 toxin (142)466C24H34O9F. oxysporum 598Baccharis spp. (Asteraceae)Brazil[105]
Trichothecenes HT-2 toxin (143)424C22H32O8F. oxysporum 598Baccharis spp. (Asteraceae)Brazil[105]
3′-OH T-2 toxin (144)482C24H34O10F. oxysporum 598Baccharis spp. (Asteraceae)Brazil[105]
Diacetoxyscirpenol (145)366C19H26O7F. oxysporum 598Baccharis spp. (Asteraceae)Brazil[105]
Phenolic and aromatics compounds
6henolic and aromati (146)300C16H12O6F. oxysporum f. sp. pisiCulturedThe Netherlands[106]
6α-Hydroxymaackiainisoflavan (147)302C16H14O6F. oxysporum f. sp. pisiCulturedThe Netherlands[106]
Pestalotiollide A (148)386C21H22O7F. oxysporumDrepanocarpus lunatus, fruit (Fabaceae) Douala, Cameroon[69]
Pestalotiollide B (149)386C21H22O7F. oxysporumDrepanocarpus lunatus, fruit (Fabaceae)Douala, Cameroon[69]
Dehydroisopenicillide (150)370C21H22O6F. oxysporumDrepanocarpus lunatus, fruit (Fabaceae)Douala, Cameroon[69]
Podophyllotoxin (151)414C22H22O8F. oxysporumJuniperus recurva,
(Cupressaceae)		Gulmarg Region,
South Kashmir, India		[107]
P-Hydroxyphenylacetate (152)152C8H8O3F. oxysporumCulturedHungary[108]
(1-Benzyl-2-methoxy-2-oxoethyl)-2-hydroxy-3-methylbutanoate (153)280C15H20O5F. oxysporum YP9BSolanum lycopersicum,
root (Solanaceae)		Pazar-Rize, Turkey[73]
Styrene (154)104C8H8F. oxysporum 13-8Prunus dulcis, hull (Rosaceae)California, USA[109]
1-Ethyl-4-methoxybenzene (155)136C9H12OF. oxysporum 13-8Prunus dulcis, hull (Rosaceae)California, USA[109]
Phenylacetic acid (156)136C8H8O2F. oxysporumCulturedHungary[108]
(+)-Fusarinolic acid (157)194C11H14O3F. oxysporumCinnamomum kanehirae, bark (Lauraceae)Jiaoban Mountain,
Taiwan. China		[65]
Pyran and furan derivatives
Chlamydosporol (158)226C11H14O5F. oxysporumMarine mudflat Suncheon Bay, Korea[70]
Gibepyrone D (159)194C10H10O4F. oxysporumCinnamomum kanehirae, bark (Lauraceae)Jiaoban Mountain,
Taiwan. China		[65]
Neovasinin (160)308C17H24O5F. oxysporum R1 and
Aspergillus fumigatus
D co-culture		-Rumex madaio
(Polygonaceae)
-Edgeworthia chrysantha (Thymelaeaceae)		China[72]
Oxysporone (161)156C7H8O4Fusarium oxysporumCulturedEngland[110]
Dihydrofuran-2(3H)-one (162)86C4H6O2F. oxysporum 13-8Prunus dulcis, hull (Rosaceae)California, USA[109]
Neovasifuranone B (163)282C16H26O4F. oxysporum R1 and Aspergillus fumigatus D co-culture-Rumex madaio
(Polygonaceae)
-Edgeworthia chrysantha (Thymelaeaceae)		China[72]
2-Pentylfuran (164)138C9H14OF. oxysporum 13-8Prunus dulcis, hull (Rosaceae)California, USA[109]
Aliphatic acids
2,3-Dihydroxypropanoic hexadecanoic anhydride (165)344C19H36O5F. oxysporum YP9BSolanum lycopersicum, root (Solanaceae)Pazar-Rize, Turkey[73]
2,3-Dihydroxypropanoic (9Z)-octadecenoic anhydride (Δ9;Z) (166)370C21H38O5F. oxysporum YP9BSolanum lycopersicum, root (Solanaceae)Pazar-Rize, Turkey[73]
2,3-Dihydroxypropanoic (9Z,12Z)-octadecadienoic anhydride (Δ9,12;Z) (167)368C21H36O5F. oxysporum YP9BSolanum lycopersicum, root (Solanaceae)Pazar-Rize, Turkey[73]
2,3-Dihydroxypropanoic (11Z)-octadecenoic anhydride (Δ11;Z) (168)370C21H38O5F. oxysporum YP9BSolanum lycopersicum, root (Solanaceae)Pazar-Rize, Turkey[73]
2,3-Dihydroxypropanoic (9E,12E)-octadecadienoic anhydride (Δ9,12;E) (169)368C21H36O5F. oxysporum YP9BSolanum lycopersicum, root (Solanaceae)Pazar-Rize, Turkey[73]
3-Hydroxy-1,2,6,10-tetramethylundecyl hexzadecanoate (170)482C31H62O3F. oxysporum YP9BSolanum lycopersicum, root (Solanaceae)Pazar-Rize, Turkey[73]
3-Hydroxy-1,2,6,10-tetramethylundecyl -octadecaenoate (Δ9;E) (171)508C33H64O3F. oxysporum YP9BSolanum lycopersicum, root (Solanaceae)Pazar-Rize, Turkey[73]
3-Hydroxy-1,2,6,10-tetramethylundecyl octadecanoate (172)510C33H66O3F. oxysporum YP9BSolanum lycopersicum, root (Solanaceae)Pazar-Rize, Turkey[73]
α-Linolenic acid (173)278C18H30O2F. oxysporum R1 and Aspergillus fumigatus D co-culture-Rumex madaio
(Polygonaceae)
-Edgeworthia chrysantha (Thymelaeaceae)		China[72]
α-Elaeostearic acid (174)278C18H30O2F. oxysporum R1 and Aspergillus fumigatus D co-culture-Rumex madaio
(Polygonaceae)
-Edgeworthia chrysantha (Thymelaeaceae)		China[72]
Palmitoleic acid (175)254C16H30O2F. oxysporum R1 and Aspergillus fumigatus D co-culture-Rumex madaio
(Polygonaceae)
-Edgeworthia chrysantha (Thymelaeaceae)		China[72]
Sugar derivatives
α-D-Mannopyranosyl-(1→2)-α-D-glucopyranosyl (176)342C12H22O11F. oxysporum L.CulturedFrance[111]
α-D-Mannopyranosyl-(1→2)-β-D-glucopyranosyl (177)342C12H22O11F. oxysporum L.CulturedFrance[111]
α-D-Mannopyranosyl-(1→X)-inositol (178)342C12H22O11F. oxysporum L.CulturedFrance[111]
Miscellaneous
Moniliformin (179)97C4HNaO3F. oxysporum 598Baccharis spp. (Asteraceae)Brazil[105]
F. oxysporumAsparagus officinalis
(Asparagaceae)		Western Poland[57]
7-Methyl-1,3,5-cyclooctatriene (MCOT) (180)120C9H12F. oxysporum 13-8Prunus dulcis, hull (Rosaceae)California, USA[109]
Table
Table 2. Biological activities of the reported metabolites from F. oxysporum.
Table 2. Biological activities of the reported metabolites from F. oxysporum.
Compound NameBiological ActivityAssay, Organism, or Cell LineBiological ResultsPositive ControlRef.
Oxysporidinone (53)AntifungalAgar diffusion/Aspergillus niger10 µg/mL (MIC)-[62]
Agar diffusion/Botrytis cinerea1 µg/mL (MIC)-[62]
Agar diffusion/Alternaria alternata50 µg/mL (MIC)-[62]
Agar diffusion/Venturia inequalis10 µg/mL (MIC)-[62]
(−)-Oxysporidinone (54)AntifungalMABA/Cryptococcus neoformans35.0 µg/mL (IC50)Amphotericin B 0.45 µg/mL (IC50)[63]
MABA/Aspergillus fumigatus2.0 µg/mL (IC50)Amphotericin B 0.91 µg/mL (IC50)[63]
(−)-4,6′-Anhydrooxysporidinone (57)AntibacterialMicrotiter plate/B. subtilis25.0 μg/mL (MIC)-[65]
Microtiter plate/MRSA100.0 μg/mL (MIC)-[65]
6-Epi-oxysporidinone (59)AntifungalMABA/Aspergillus fumigatus35.0 µg/mL (IC50)Amphotericin B 0.91 µg/mL (IC50)[63]
Fusaric acid (63)AntimicrobialMicrotitre plate/Colletotrichum coccodes81.0 µg/mL (IC50)DMSO 1%[66]
Microtitre plate/Magnaporthe grisea50.0 µg/mL (IC50)DMSO 1%[66]
Microtitre plate/Phytophthora capsici0.36 µg/mL (IC50)DMSO 1%[66]
Microtitre plate/Phytophthora infestans1.0 µg/mL (IC50)DMSO 1%[66]
Microtitre plate/Rhizoctonia solani11.0 µg/mL (IC50)DMSO 1%[66]
Microtitre plate/Acidovorax konjaci0.2 µg/mL (IC50)DMSO 1%[66]
Microtitre plate/Agrobacterium tumefaciens3.0 µg/mL (IC50)DMSO 1%[66]
Microtitre plate/Burkholderia glumae1.7 µg/mL (IC50)DMSO 1%[66]
Microtitre plate/Pectobacterium carotovora ssp. carotovora12.0 µg/mL (IC50)DMSO 1%[66]
Microtitre plate/Pseudomonas syringae pv. lachrymans11.0 µg/mL (IC50)DMSO 1%[66]
Microtitre plate/Xanthomonas euvesicatoria0.2 µg/mL (IC50)DMSO 1%[66]
Fusaricate B (66)CytotoxicityMTT/L5178Y37.7 µM (IC50)Kahalalide F 4.3 µM (IC50)[69]
Oxysporizoline (73)AntioxidantDPPH10 μM (IC50)Ascorbic acid 20 μM (IC50)[70]
Butenolide (75)AntioxidantDPPH12 μM (IC50)Ascorbic acid 20 μM (IC50)[70]
2-Oxo-8-azatricyclo[9.3.1.13,7]-hexadeca
-1(15),3(16),4,6,11,13-hexaen-10-one (80)		AntimicrobialDouble microdilution/Escherichia coli ATCC259221.6 µg/mL (MIC)Ampicillin 10 µg/mL (MIC)[73]
Double microdilution/Yersinia pseudotuberculosis ATCC9111.6 µg/mL (MIC)Ampicillin 18 µg/mL (MIC)[73]
Double microdilution/Klebsiella pneumonia subsp.
pneumonia ATCC13883		1.6 µg/mL (MIC)Ampicillin 18 µg/mL (MIC)[73]
Double microdilution/Pseudomonas
aeruginosa ATCC27853		1.6 µg/mL (MIC)Ampicillin >128 µg/mL (MIC)[73]
Double microdilution/Staphylococcus aureus ATCC259230.8 µg/mL (MIC)Ampicillin 10 µg/mL (MIC)[73]
Double microdilution/Enterococcus faecalis ATCC292121.6 µg/mL (MIC)Ampicillin 35 µg/mL (MIC)[73]
Double microdilution/Streptococcus mutans RSKK070386.3 µg/mL (MIC)-[73]
Double microdilution/Lactobacillus casei RSK59112.5 µg/mL (MIC)-[73]
Double microdilution/Bacillus cereus 702 Roma0.8 µg/mL (MIC)Ampicillin 15 µg/mL (MIC)[73]
Double microdilution/Mycobacterium
smegmatis ATCC607		3.1 µg/mL (MIC)Streptomycin 4 µg/mL (MIC)[73]
Double microdilution/Candida albicans ATCC601933.1 µg/mL (MIC)Fluconazole < 8 µg/mL (MIC)[73]
Double microdilution/C. tropicalis ATTCC 138033.1 µg/mL (MIC)Fluconazole < 8 µg/mL (MIC)[73]
Double microdilution/Saccharomyces cerevisiae RSKK2516.3 µg/mL (MIC)Fluconazole < 8 µg/mL (MIC)[73]
Fusarioxazin (81)CytotoxicityMTT/MCF-72.1 µM (IC50)Doxorubicin 0.68 µM (IC50)[18]
MTT/HCT1164.7 µM (IC50)Doxorubicin 1.34 µM (IC50)[18]
MTT/A5493.2 µM (IC50)Doxorubicin 0.39 µM (IC50)[18]
AntimicrobialDisc diffusion/S. aureus5.3 µg/mL (MIC)Ciprofloxacin 3.9 µg/mL (MIC)[18]
Disc diffusion/B. cereus3.7 µg/mL (MIC)Ciprofloxacin 2.3 µg/mL (MIC)[18]
Disc diffusion/E. coli15.9 µg/mL (MIC)Ciprofloxacin 4.1 µg/mL (MIC)[18]
Disc diffusion/C. albicans18.2 µg/mL (MIC)Clotrimazole 3.5 µg/mL (MIC)[18]
Epi-trichosetin (82)Inhibition of UPP synthaseEnzyme-coupled fluorescent/S. aureus83.0 µM (IC50)-[74]
AntimicrobialDisc diffusion/S. aureus ATCC 6538P (MSSA)18.0 mm (IZD)-[74]
Disc diffusion/S. aureus K24 (MRSA)16.0 mm (IZD)-[74]
Disc diffusion/Bacillus subtilis PCI 21918.0 mm (IZD)-[74]
Disc diffusion/Micrococcus luteus PCI 934117.0 mm (IZD)-[74]
Disc diffusion/Mycobacterium smegmatis ATCC 6079.0 mm (IZD)-[74]
Disc diffusion/Escherichia coli NIHJ10.0 mm (IZD)-[74]
Disc diffusion/Xanthomonas campestris KB 889.0 mm (IZD)-[74]
Disc diffusion/Bacteroides fragilis ATCC 2374511.0 mm (IZD)-[74]
Disc diffusion/Acholeplasma laidlawii KB 17412.0 mm (IZD)-[74]
Disc diffusion/Pyricularia oryzae KF 18014.0 mm (IZD)-[74]
Disc diffusion/Mucor racemosus IFO 45817.0 mm (IZD)-[74]
Trichosetin (83)Inhibition of UPP synthaseEnzyme-coupled fluorescent/S. aureus30.0 µM (IC50)-[74]
AntimicrobialDisc diffusion/S. aureus ATCC 6538P (MSSA)15.0 mm (IZD)-[74]
Disc diffusion/S. aureus K24 (MRSA)14.0 mm (IZD)-[74]
Disc diffusion/Bacillus subtilis PCI 21916.0 mm (IZD)-[74]
Disc diffusion/Micrococcus luteus PCI 934115.0 mm (IZD)-[74]
Disc diffusion/Mycobacterium smegmatis ATCC 6078.0 mm (IZD)-[74]
Disc diffusion/Escherichia coli NIHJ10.0 mm (IZD)-[74]
Disc diffusion/Xanthomonas campestris KB 887.0 mm (IZD)-[74]
Disc diffusion/Bacteroides fragilis ATCC 2374511.0 mm (IZD)-[74]
Disc diffusion/Acholeplasma laidlawii KB 1749.0 mm (IZD)-[74]
Disc diffusion/Pyricularia oryzae KF 18011.0 mm (IZD)-[74]
Disc diffusion/Mucor racemosus IFO 45817.0 mm (IZD)-[74]
Enniatin A (91)AntifungalMABA/Candida albicans2.0 µg/mL (IC50)Amphotericin B 0.35 µg/mL (IC50)[63]
MABA/Cryptococcus neoformans3.5 µg/mL (IC50)Amphotericin B 0.45 µg/mL (IC50)[63]
MABA/Mycobacterium intracellulare5.0 µg/mL (IC50)Ciprofloxacin 0.3 µg/mL (IC50)[63]
Enniatin A1 (92)AntifungalMABA/Candida albicans2.0 µg/mL (IC50)Amphotericin B 0.35 µg/mL (IC50)[63]
MABA/Cryptococcus neoformans4.5 µg/mL (IC50)Amphotericin B 0.45 µg/mL (IC50)[63]
MABA/Mycobacterium intracellulare9.0 µg/mL (IC50)Ciprofloxacin 0.3 µg/mL (IC50)[63]
Enniatin B1 (93)AntifungalMABA/Candida albicans2.0 µg/mL (IC50)Amphotericin B 0.35 µg/mL (IC50)[63]
MABA/Cryptococcus neoformans9.0 µg/mL (IC50)Amphotericin B 0.45 µg/mL (IC50)[63]
MABA/Mycobacterium intracellulare15.0 µg/mL (IC50)Ciprofloxacin 0.3 µg/mL (IC50)[63]
Enniatin H (96)CytotoxicitySRB/A5491.84 µM (EC50)Doxorubicin 0.03 µM (EC50)[83]
SRB/SK-OV-31.71 µM (EC50)Doxorubicin 0.06 µM (EC50)[83]
SRB/SK-MEL-21.77 µM (EC50)Doxorubicin 0.04 µM (EC50)[83]
SRB/HCT152.45 µM (EC50)Doxorubicin 0.2 µM (EC50)[83]
Enniatin I (97)CytotoxicitySRB/A5490.50 µM (EC50)Doxorubicin 0.03 µM (EC50)[83]
SRB/SK-OV-30.49 µM (EC50)Doxorubicin 0.06 µM (EC50)[83]
SRB/SK-MEL-20.53 µM (EC50)Doxorubicin 0.04 µM (EC50)[83]
SRB/HCT150.53 µM (EC50)Doxorubicin 0.2 µM (EC50)[83]
Enniatin MK1688 (98)CytotoxicitySRB/A5490.45 µM (EC50)Doxorubicin 0.03 µM (EC50)[83]
SRB/SK-OV-30.45 µM (EC50)Doxorubicin 0.06 µM (EC50)[83]
SRB/SK-MEL-20.63 µM (EC50)Doxorubicin 0.04 µM (EC50)[83]
SRB/HCT150.53 µM (EC50)Doxorubicin 0.2 µM (EC50)[83]
Beauvericin (99)CytotoxicityMTT/NCI-H4600.43 µM (IC50)Doxorubicin 0.01 µM (IC50)[64]
MTT/MIA Pa Ca-20.26 µM (IC50)Doxorubicin 0.05 µM (IC50)[64]
MTT/MCF-70.42 µM (IC50)Doxorubicin 0.07 µM (IC50)[64]
MTT/SF-2680.38 µM (IC50)Doxorubicin 0.04 µM (IC50)[64]
SRB/A5491.43 µM (EC50)Doxorubicin 0.03 µM (EC50)[83]
SRB/SK-OV-31.39 µM (EC50)Doxorubicin 0.06 µM (EC50)[83]
SRB/SK-MEL-21.47 µM (EC50)Doxorubicin 0.04 µM (EC50)[83]
SRB/HCT151.86 µM (EC50)Doxorubicin 0.2 µM (EC50)[83]
MTT/PC-349.5 µM (IC50)Cisplatin 26.8 µM (IC50)[65]
MTT/ PANC-147.2 µM (IC50)Cisplatin 26.2 µM (IC50)[65]
MTT/A54910.4 µM (IC50)Cisplatin 19.8 µM (IC50)[65]
MTT/HCT-83.02 µg/mL (IC50)Doxorubicin 0.04 µg/mL (IC50)[84]
MTT/MDA-MB4353.17 µg/mL (IC50)Doxorubicin 0.2 µg/mL (IC50)[84]
MTT/SF2952.39 µg/mL (IC50)Doxorubicin 0.04 µg/mL (IC50)[84]
Antibacterial Microtiter plate/MRSA3.125 μg/mL (MIC)-[65]
Microtiter plate/B. subtilis3.125 μg/mL (MIC)-[65]
LeishmanicidalMTT (anti-promastigote)/L. braziliensis strain H3227 (MHOM/BR/94/H-3227)1.86 μM (EC50)Geneticin 0.007 HOM/EC50)[84]
Anhydrofusarubin (105)CytotoxicityMTT/HCT-89.85 µg/mL (IC50)Doxorubicin 0.04 µg/mL (IC50)[84]
MTT/MDA-MB4356.23 µg/mL (IC50)Doxorubicin 0.2 µg/mL (IC50)[84]
MTT/SF2956.32 µg/mL (IC50)Doxorubicin 0.04 µg/mL (IC50)[84]
Plant nematicidalAntinemic/Meloidogyne incognita257.6 µg/mL (LC50)Carbofuran 54.2 µg/mL (LC50)[88]
Antinemic/Rotylenchulus reniformis285.3 µg/mL (LC50)Carbofuran 37.6 µg/mL (LC50)[88]
Fusarubin (107)Plant nematicidalAntinemic/Meloidogyne incognita248.9 µg/mL (LC50)Carbofuran 54.2 µg/mL (LC50)[88]
Antinemic/Rotylenchulus reniformis301.6 µg/mL (LC50)Carbofuran 37.6 µg/mL (LC50)[88]
8-O-methylfusarubin (108) = 9-O-MethylfusarubinPlant nematicidalAntinemic/Meloidogyne incognita376.4 µg/mL (LC50)Carbofuran 54.2 µg/mL (LC50)[88]
Antinemic/Rotylenchulus reniformis518.4 µg/mL (LC50)Carbofuran 37.6 µg/mL (LC50)[88]
3-O-Methyl-8-O-methylfusarubin (109) = 3-O-Methyl-9-O-methylfusarubinPlant nematicidalAntinemic/Meloidogyne incognita478.5 µg/mL (LC50)Carbofuran 54.2 µg/mL (LC50)[88]
Antinemic/Rotylenchulus reniformis465.2 µg/mL (LC50)Carbofuran 37.6 µg/mL (LC50)[88]
8-O-Methyljavanicin (111)AntibacterialMicrodilution/S. aureus4 µg/mL (MIC)-[90]
Microdilution/Streptococcus
pyogenes		>128 µg/mL (MIC)-[90]
8-O-Methylsolaniol (112)AntibacterialMicrodilution/S. aureus32.0 µg/mL (MIC)-[90]
Microdilution/Streptococcus
pyogenes		64.0 µg/mL (MIC)-[90]
Nectriafurone (114)AntibacterialMicrodilution/S. aureus>128 µg/mL (MIC)-[90]
Microdilution/Streptococcus
pyogenes		128 µg/mL (MIC)-[90]
Bikaverin (119)Antimicrobial Microtitre plate/Colletotrichum coccodes70.0 µg/mL (IC50)DMSO 1%[66]
Microtitre plate/Magnaporthe grisea70.0 µg/mL (IC50)DMSO 1%[66]
Microtitre plate/Phytophthora capsici10.0 µg/mL (IC50)DMSO 1%[66]
Microtitre plate/Phytophthora infestans60.0 µg/mL (IC50)DMSO 1%[66]
CytotoxicityMTT/NCI-H4601.41 µM (IC50)Doxorubicin 0.01 µM (IC50)[64]
MTT/MIA Pa Ca-21.66 µM (IC50)Doxorubicin 0.05[64]
MTT/MCF-71.81 µM (IC50)Doxorubicin 0.07 µM (IC50)[64]
MTT/SF-2682.29 µM (IC50)Doxorubicin 0.04 µM (IC50)[64]
NematicidalAntinemic/Meloidogyne incognita392.9 µg/mL (LC50)Carbofuran 54.2 µg/mL (LC50)[88]
Antinemic/Rotylenchulus reniformis618.0 µg/mL (LC50)Carbofuran 37.6 µg/mL (LC50)[88]
Wortmannin (129)AntifungalMABA/Candida albicans0.25 µg/mL (IC50)Amphotericin B 0.35 µg/mL (IC50)[63]
H1-A = Ergosta-5,8 (14),22-trien-7-one, 3-hydroxy-(3β, 22E) (130)Anti-hepatitis C virus (HCV) NS3 serine proteaseFRET/HCV NS3 protease99.7 μM/L (Ki value)VX950 3.5 μM/L (Ki value)[99]
Fusariumins C (135)AntimicrobialMicrobroth dilution/S. aureus6.25 μM (MIC)Ampicillinum
sodium		[102]
Fusariumins D (136)AntimicrobialMicrobroth dilution/S. aureus25 μM (MIC)Ampicillinum
sodium		[102]
(1-Benzyl-2-methoxy-2-oxoethyl)-2-hydroxy-3-methylbutanoate (153)CytotoxicityMTT/MCF-715.01 µM (IC50)Doxorubicin 0.053 µM (IC50)[73]
MTT/PC-319.13 µM (IC50)Doxorubicin 0.09 µM (IC50)[73]
MTT/A54917.06 µM (IC50)Doxorubicin 17.75 µM (IC50)[73]
AntimicrobialDouble microdilution/Escherichia coli ATCC2592260 µg/mL (MIC)Ampicillin 10 µg/mL (MIC)[73]
Double microdilution/Yersinia pseudotuberculosis ATCC91160 µg/mL (MIC)Ampicillin 18 µg/mL (MIC)[73]
Double microdilution/Klebsiella pneumonia subsp. pneumonia ATCC1388360 µg/mL (MIC)Ampicillin 18 µg/mL (MIC)[73]
Double microdilution/Pseudomonas aeruginosa ATCC2785360 µg/mL (MIC)Ampicillin >128 µg/mL (MIC)[73]
Double microdilution/Staphylococcus aureus ATCC259230.94 µg/mL (MIC)Ampicillin 10 µg/mL (MIC)[73]
Double microdilution/Enterococcus faecalis ATCC292121.8 µg/mL (MIC)Ampicillin 35 µg/mL (MIC)[73]
Double microdilution/Streptococcus mutans RSKK070381.8 µg/mL (MIC)-[73]
Double microdilution/Lactobacillus casei RSK59130 µg/mL (MIC)-[73]
Double microdilution/Bacillus cereus 702 Roma0.94 µg/mL (MIC)Ampicillin 15 µg/mL (MIC)[73]
Double microdilution/Mycobacterium
smegmatis ATCC607		0.47 µg/mL (MIC)Streptomycin 4 µg/mL (MIC)[73]
Double microdilution/Candida albicans ATCC6019360 µg/mL (MIC)Fluconazole < 8 µg/mL (MIC)[73]
Double microdilution/C. tropicalis ATTCC 1380360 µg/mL (MIC)Fluconazole < 8 µg/mL (MIC)[73]
Double microdilution/Saccharomyces cerevisiae RSKK251120 µg/mL (MIC)Fluconazole < 8 µg/mL (MIC)[73]
Mixture of 2,3-dihydroxypropanoic (11Z)-octadecenoic anhydride (168) and 2,3-dihydroxypropanoic, (9E,12E)-octadecadienoic anhydride (169)AntimicrobialDouble microdilution/E. coli ATCC259227.8 µg/mL (MIC)Ampicillin 10 µg/mL (MIC)[73]
Double microdilution/Yersinia
pseudotuberculosis ATCC911		7.7 µg/mL (MIC)Ampicillin 18 µg/mL (MIC)[73]
Double microdilution/Klebsiella pneumonia subsp.
pneumonia ATCC13883		7.7 µg/mL (MIC)Ampicillin 18 µg/mL (MIC)[73]
Double microdilution/Pseudomonas
aeruginosa ATCC27853		7.7 µg/mL (MIC)Ampicillin > 128 µg/mL (MIC)[73]
Double microdilution/Staphylococcus aureus ATCC259233.8 µg/mL (MIC)Ampicillin 10 µg/mL (MIC)[73]
Double microdilution/Enterococcus faecalis ATCC292127.7 µg/mL (MIC)Ampicillin 35 µg/mL (MIC)[73]
Double microdilution/Streptococcus mutans RSKK0703830.6 µg/mL (MIC)-[73]
Double microdilution/Lactobacillus casei RSK59161.2 µg/mL (MIC)-[73]
Double microdilution/Bacillus cereus 702 Roma7.7 µg/mL (MIC)Ampicillin 15 µg/mL (MIC)[73]
Double microdilution/Mycobacterium
smegmatis ATCC607		30.6 µg/mL (MIC)Streptomycin 4 µg/mL (MIC)[73]
Double microdilution/C. albicans ATCC6019330.6 µg/mL (MIC)Fluconazole < 8 µg/mL (MIC)[73]
Double microdilution/C. tropicalis ATTCC 1380330.6 µg/mL (MIC)Fluconazole < 8 µg/mL (MIC)[73]
Double microdilution/Saccharomyces cerevisiae RSKK25130.6 µg/mL (MIC)Fluconazole < 8 µg/mL (MIC)[73]
Mixture of 3-hydroxy-1,2,6,10-tetramethylundecyl hexzadecanoate (170), 3-hydroxy-1,2,6,10-tetramethylundecyl (9E)-octadecaenoate (171), and 3-hydroxy-1,2,6,10-tetramethylundecyl octadecanoate (172)CytotoxicityMTT/MCF-77.75 µM (IC50)Doxorubicin 0.053 µM (IC50)[73]
MTT/PC-317.75 µM (IC50)Doxorubicin 0.09 µM (IC50)[73]
MTT/A5497.51 µM (IC50)Doxorubicin 17.75 µM (IC50)[73]
AntimicrobialDouble microdilution/S. aureus ATCC259234.3 µg/mL (MIC)Ampicillin 10 µg/mL (MIC)[73]
Double microdilution/Enterococcus faecalis ATCC292124.3 µg/mL (MIC)Ampicillin 35 µg/mL (MIC)[73]
Double microdilution/Streptococcus mutans RSKK070384.3 µg/mL (MIC)-[73]
Double microdilution/Bacillus cereus 702 Roma2.1 µg/mL (MIC)Ampicillin 15 µg/mL (MIC)[73]
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MDPI and ACS Style

Ibrahim, S.R.M.; Sirwi, A.; Eid, B.G.; Mohamed, S.G.A.; Mohamed, G.A. Bright Side of Fusarium oxysporum: Secondary Metabolites Bioactivities and Industrial Relevance in Biotechnology and Nanotechnology. J. Fungi 2021, 7, 943. https://doi.org/10.3390/jof7110943

AMA Style

Ibrahim SRM, Sirwi A, Eid BG, Mohamed SGA, Mohamed GA. Bright Side of Fusarium oxysporum: Secondary Metabolites Bioactivities and Industrial Relevance in Biotechnology and Nanotechnology. Journal of Fungi. 2021; 7(11):943. https://doi.org/10.3390/jof7110943

Chicago/Turabian Style

Ibrahim, Sabrin R. M., Alaa Sirwi, Basma G. Eid, Shaimaa G. A. Mohamed, and Gamal A. Mohamed. 2021. "Bright Side of Fusarium oxysporum: Secondary Metabolites Bioactivities and Industrial Relevance in Biotechnology and Nanotechnology" Journal of Fungi 7, no. 11: 943. https://doi.org/10.3390/jof7110943

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