Secondary Metabolism of Microorganisms 2.0

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Microbial Biotechnology".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 19030

Special Issue Editors


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Guest Editor
Área de Bioquímica y Biología Molecular, Departamento de Biología Molecular, Universidad de León, 24007 León, Spain
Interests: secondary metabolites; microorganisms; proteomics; plastics; actinobacteria; fungi; carotenoids; steroids; immunosuppressors; antibiotics
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
1. Instituto de Biotecnología de León (INBIOTEC), León, Spain
2. Departamento de Ciencias Biomédicas, Facultad de Veterinaria, Campus de Vegazana, Universidad de León, 24071 León, Spain
Interests: fungal secondary metabolism; molecular biology; biotechnology; genetic engineering; omics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our previous special issue "Secondary Metabolism of Microorganisms".

Microbial secondary metabolism represents a very interesting research field. On the one hand, secondary metabolism is considered nonessential for microbial growth and development, but it results in the biosynthesis of an impressive array of compounds relevant for i) human and animal health (e.g., antibiotics, receptor antagonists and agonists, immunosuppressants), ii) food and feed (e.g., pigments), iii) agriculture (e.g., pheromones, plant protectants), and iv) farming (e.g., toxins). This industrially relevant group of compounds is produced by certain taxonomic clades of organisms such as bacteria, mainly Actinobacteria, and fungi. Since metabolite formation is usually repressed during the logarithmic phase of growth and boosted along the stationary growth phase, a regulatory fine-tuning of nutrients (e.g., phosphate, nitrogen), precursors, and energy molecules is needed. The understanding of this strictly controlled process opens the door to synthetic biology to redirect metabolic pathways, avoiding nutrient sinks and by-products generation.

On the other hand, secondary metabolism plays a significant ecological role in the communication among different microorganisms in nature. At present, mixed fermentation or co-cultivation is a trending manner in order to study, understand, and harness the microbial competition and communication when the appropriate physiological conditions are provided.

This Special Issue of Microorganisms invites researchers to contribute research articles, reviews, and opinions addressing the latest knowledge on the secondary metabolism of microorganisms, including molecular biology, omics, synthetic biology, industrial microbiology, genome editing, metabolites production, downstream processing, gene control and regulation, etc., both in fundamental research and its applications. This Special Issue is divided into three blocks: i) microbial secondary metabolites; ii) regulation of secondary metabolism; and iii) communication of microbial communities. Manuscripts covering these areas of knowledge, and others related to microbial secondary metabolism, are of interest for this Special Issue.

Dr. Carlos Barreiro
Dr. Carlos García-Estrada
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • secondary metabolites

  • industrial microbiology
  • microbial communication
  • metabolism regulation
  • genome editing
  • human and animal health
  • food and feed additives
  • biocontrol

Published Papers (9 papers)

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Research

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12 pages, 3139 KiB  
Article
Response Surfaces Method and Artificial Intelligence Approaches for Modeling the Effects of Environmental Factors on Chlorophyll a in Isochrysis galbana
by Linlin Zhang, Jie Liu, Xin Shen, Shuangwei Li, Wenfang Li and Xinfeng Xiao
Microorganisms 2023, 11(8), 1875; https://doi.org/10.3390/microorganisms11081875 - 25 Jul 2023
Cited by 1 | Viewed by 804
Abstract
This study reported the condition optimization for chlorophyll a (Chl a) from the microalga Isochrysis galbana. The key parameters affecting the Chl a content of I. galbana were determined by a single-factor optimization experiment. Then the individual and interaction of [...] Read more.
This study reported the condition optimization for chlorophyll a (Chl a) from the microalga Isochrysis galbana. The key parameters affecting the Chl a content of I. galbana were determined by a single-factor optimization experiment. Then the individual and interaction of three factors, including salinity, pH and nitrogen concentration, was optimized by using the method of Box–Benhnken Design. The highest Chl a content (0.51 mg/L) was obtained under the optimum conditions of salinity 30‰ and nitrogen concentration of 72.1 mg/L at pH 8.0. The estimation models of Chl a content based on the response surfaces method (RSM) and three different artificial intelligence models of artificial neural network (ANN), support vector machine (SVM) and radial basis function neural network (RBFNN), were established, respectively. The fitting model was evaluated by using statistical analysis parameters. The high accuracy of prediction was achieved on the ANN, SVM and RBFNN models with correlation coefficients (R2) of 0.9113, 0.9127, and 0.9185, respectively. The performance of these artificial intelligence models depicted better prediction capability than the RSM model for anticipating all the responses. Further experimental results suggested that the proposed SVM and RBFNN model are efficient techniques for accurately fitting the Chl a content of I. galbana and will be helpful in validating future experimental work on the Chl a content by computational intelligence approach. Full article
(This article belongs to the Special Issue Secondary Metabolism of Microorganisms 2.0)
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11 pages, 1868 KiB  
Article
Volatile Metabolites from Brevundimonas diminuta and Nematicidal Esters Inhibit Meloidogyne javanica
by Yongxiang Sun, Yuan Ran, Hanbo Yang, Minghe Mo and Guohong Li
Microorganisms 2023, 11(4), 966; https://doi.org/10.3390/microorganisms11040966 - 7 Apr 2023
Cited by 2 | Viewed by 1599
Abstract
Brevundimonas diminuta is broadly distributed in terrestrial and aquatic environments and has various biological activities. In this study, we found that B. diminuta exhibited nematicidal activity against the plant root-knot nematode, Meloidogyne javanica. A total of 42 volatile organic compounds (VOCs) from [...] Read more.
Brevundimonas diminuta is broadly distributed in terrestrial and aquatic environments and has various biological activities. In this study, we found that B. diminuta exhibited nematicidal activity against the plant root-knot nematode, Meloidogyne javanica. A total of 42 volatile organic compounds (VOCs) from B. diminuta were identified using gas chromatography–mass spectrometry (GC-MS). The nematicidal activity of the 10 main VOCs was tested against M. javanica. Butyl butanoate (4 µL) caused the mortality of 80.13% of M. javanica after 4 h. The nematicidal activity of an additional 38 butyl-butyrate-like volatile esters was also investigated. Of these, seven had strong nematicidal activity against M. javanica, five of which showed egg-hatching inhibitory activity. This study is the first to report that butyl butanoate, ethyl 2-methylbutanoate, ethyl 4-methylpentanoate, ethyl pent-4-enoate, and methyl undecanoate have nematicidal activity against M. javanica. The results indicated that B. diminuta could serve as a candidate microorganism for the biocontrol of plant root-knot nematodes, showing that volatile esters have great potential as nematicides. Full article
(This article belongs to the Special Issue Secondary Metabolism of Microorganisms 2.0)
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14 pages, 30661 KiB  
Article
The Potential of Bacilli-Derived Biosurfactants as an Additive for Biocontrol against Alternaria alternata Plant Pathogenic Fungi
by Jesse John Sakiyo and Áron Németh
Microorganisms 2023, 11(3), 707; https://doi.org/10.3390/microorganisms11030707 - 9 Mar 2023
Cited by 3 | Viewed by 1616
Abstract
Fungal diseases caused by Alternaria alternata constitute a significant threat to the production and quality of a wide range of crops, including beans, fruits, vegetables, and grains. Traditional methods for controlling these diseases involve synthetic chemical pesticides, which can negatively impact the environment [...] Read more.
Fungal diseases caused by Alternaria alternata constitute a significant threat to the production and quality of a wide range of crops, including beans, fruits, vegetables, and grains. Traditional methods for controlling these diseases involve synthetic chemical pesticides, which can negatively impact the environment and human health. Biosurfactants are natural, biodegradable secondary metabolites of microorganisms that have also been shown to possibly have antifungal activity against plant pathogenic fungi, including A. alternata being sustainable alternatives to synthetic pesticides. In this study, we investigated the potential of biosurfactants of three bacilli (Bacillus licheniformis DSM13, Bacillus subtilis DSM10, and Geobacillus stearothermophilus DSM2313) as a biocontrol agent against A. alternata on beans as a model organism. For this fermentation, we describe using an in-line biomass sensor monitoring both permittivity and conductivity, which are expected to correlate with cell concentration and products, respectively. After the fermentation of biosurfactants, we first characterised the properties of the biosurfactant, including their product yield, surface tension decrement capability, and emulsification index. Then, we evaluated the antifungal properties of the crude biosurfactant extracts against A. alternata, both in vitro and in vivo, by analysing various plant growth and health parameters. Our results showed that bacterial biosurfactants effectively inhibited the growth and reproduction of A. alternata in vitro and in vivo. B. licheniformis manufactured the highest amount of biosurfactant (1.37 g/L) and demonstrated the fastest growth rate, while G. stearothermophilus produced the least amount (1.28 g/L). The correlation study showed a strong positive relationship between viable cell density VCD and OD600, as well as a similarly good positive relationship between conductivity and pH. The poisoned food approach in vitro demonstrated that all three strains suppressed mycelial development by 70–80% when applied with the highest tested dosage of 30%. Regarding in vivo investigations, B. subtilis post-infection treatment decreased the disease severity to 30%, whereas B. licheniformis and G. stearothermophilus post-infection treatment reduced disease severity by 25% and 5%, respectively. The study also revealed that the plant’s total height, root length, and stem length were unaffected by the treatment or the infection. Full article
(This article belongs to the Special Issue Secondary Metabolism of Microorganisms 2.0)
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12 pages, 2448 KiB  
Article
Nematicidal Metabolites from the Actinomycete Micromonospora sp. WH06
by Yuan Ran, Yu Zhang, Xin Wang and Guohong Li
Microorganisms 2022, 10(11), 2274; https://doi.org/10.3390/microorganisms10112274 - 16 Nov 2022
Cited by 1 | Viewed by 2148
Abstract
A nematicidal actinomycete strain WH06 was isolated from soil samples and was identified using 16S rRNA as Micromonospora sp. Through medium screening and fermentation, 10 metabolites were isolated from the ethyl acetate extract of its fermentation broth using Sephadex LH-20 and silica gel [...] Read more.
A nematicidal actinomycete strain WH06 was isolated from soil samples and was identified using 16S rRNA as Micromonospora sp. Through medium screening and fermentation, 10 metabolites were isolated from the ethyl acetate extract of its fermentation broth using Sephadex LH-20 and silica gel column chromatography. These compounds were identified as N-acetyltyramine (1), N-acetyltryptamine (2), 1-methylhydantoin (3), benzenepropanoic acid (4), cyclo-(L-Pro-L-Tyr) (5), cyclo(L-Phe-Gly) (6), catechol (7), methyl (4-hydroxyphenyl)acetate (8), 3-hydroxybenzoic acid (9), and 4-hydroxybenzoic acid (10). In an in vitro assay against Meloidogyne incognita, a root-knot nematode, compounds 1, 4, 9, and 10 show nematicidal activity. Among them, benzenepropanoic acid (4) causes 99.02% mortality of nematode at 200 μg mL−1 after 72 h. Moreover, compound 4 also displays activity in inhibiting egg hatching of M. incognita. This suggests that Micromonospora sp. WH06 is a promising candidate for biocontrol of M. incognita. Full article
(This article belongs to the Special Issue Secondary Metabolism of Microorganisms 2.0)
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13 pages, 4839 KiB  
Article
Whole-Genome Sequence Analysis of an Endophytic Fungus Alternaria sp. SPS-2 and Its Biosynthetic Potential of Bioactive Secondary Metabolites
by Jianyun Tao, Xuelian Bai, Mingyuan Zeng, Mengshi Li, Zhe Hu, Yunfen Hua and Huawei Zhang
Microorganisms 2022, 10(9), 1789; https://doi.org/10.3390/microorganisms10091789 - 5 Sep 2022
Cited by 5 | Viewed by 2268
Abstract
As one of the commonly isolated endophytic fungi, Alternaria has been known for the production of numerous secondary metabolites (SMs). However, its detailed genomic features and SM biosynthetic potential have not been extensively studied thus far. The present work focuses on the whole-genome [...] Read more.
As one of the commonly isolated endophytic fungi, Alternaria has been known for the production of numerous secondary metabolites (SMs). However, its detailed genomic features and SM biosynthetic potential have not been extensively studied thus far. The present work focuses on the whole-genome sequencing and assembly of an endophytic strain Alternaria sp. SPS-2 derived from Echrysantha chrysantha Lindl. and gene annotation using various bioinformatic tools. The results of this study suggested that the genome of strain SPS-2 was 33.4 Mb in size with a GC content of 51% and an N50 scaffold of 2.6 Mb, and 9789 protein-coding genes, including 644 CAZyme-encoding genes, were discovered in strain SPS-2 through KEGG enrichment analysis. The antiSMASH results indicated that strain SPS-2 harbored 22 SM biosynthetic gene clusters (BGCs), 14 of which are cryptic and unknown. LS–MS/MS and GNPS-based analyses suggested that this endophytic fungus is a potential producer of bioactive SMs and merits further exploration and development. Full article
(This article belongs to the Special Issue Secondary Metabolism of Microorganisms 2.0)
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9 pages, 1957 KiB  
Article
Secondary Metabolites from the Endoparasitic Nematophagous Fungus Harposporium anguillulae YMF 1.01751
by Zebao Dai, Yang Gan, Peiji Zhao and Guohong Li
Microorganisms 2022, 10(8), 1553; https://doi.org/10.3390/microorganisms10081553 - 31 Jul 2022
Viewed by 1779
Abstract
Harposporium anguillulae, an endoparasitic nematophagous fungus (ENF), is a model fungus from which the genus Harposporium was established. It can infect nematodes via ingested conidia. In this paper, the morphology and nematode–fungus interaction between Panagrellus redivivus and H. anguillulae were observed by [...] Read more.
Harposporium anguillulae, an endoparasitic nematophagous fungus (ENF), is a model fungus from which the genus Harposporium was established. It can infect nematodes via ingested conidia. In this paper, the morphology and nematode–fungus interaction between Panagrellus redivivus and H. anguillulae were observed by scanning electron microscopy (SEM). The secondary metabolites of H. anguillulae were also studied. Seven metabolites were purified and identified from an ethyl acetate extract of broth and a methanol extract of mycelium. These include a new polyketone 5-hydroxy-3-(hydroxymethyl)-6-methyl-2H-pyran-2-one (1) and six known metabolites (17R)-17-methylincisterol (2), eburicol (3), ergosterol peroxide (4), terpendole C (5), (3β,5α,9β,22E)-3,5-dihydroxy-ergosta-7,22-dien-6-one (6), and 5α,6β-epoxy-(22E,24R)-ergosta-8,22-diene- 3β,7α-diol (7). These metabolites were assayed for their activity against plant root-knot nematode, Meloidogyne incognita, and the results showed that terpendole C (5) had weak nematicidal activity but also that other compounds did not have evident activity at a concentration of 400 μg mL1. Compound 1 exhibited an attractive effect towards P. redivivus. Full article
(This article belongs to the Special Issue Secondary Metabolism of Microorganisms 2.0)
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Review

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17 pages, 2871 KiB  
Review
Uses of Multi-Objective Flux Analysis for Optimization of Microbial Production of Secondary Metabolites
by Marc Griesemer and Ali Navid
Microorganisms 2023, 11(9), 2149; https://doi.org/10.3390/microorganisms11092149 - 24 Aug 2023
Cited by 2 | Viewed by 1256
Abstract
Secondary metabolites are not essential for the growth of microorganisms, but they play a critical role in how microbes interact with their surroundings. In addition to this important ecological role, secondary metabolites also have a variety of agricultural, medicinal, and industrial uses, and [...] Read more.
Secondary metabolites are not essential for the growth of microorganisms, but they play a critical role in how microbes interact with their surroundings. In addition to this important ecological role, secondary metabolites also have a variety of agricultural, medicinal, and industrial uses, and thus the examination of secondary metabolism of plants and microbes is a growing scientific field. While the chemical production of certain secondary metabolites is possible, industrial-scale microbial production is a green and economically attractive alternative. This is even more true, given the advances in bioengineering that allow us to alter the workings of microbes in order to increase their production of compounds of interest. This type of engineering requires detailed knowledge of the “chassis” organism’s metabolism. Since the resources and the catalytic capacity of enzymes in microbes is finite, it is important to examine the tradeoffs between various bioprocesses in an engineered system and alter its working in a manner that minimally perturbs the robustness of the system while allowing for the maximum production of a product of interest. The in silico multi-objective analysis of metabolism using genome-scale models is an ideal method for such examinations. Full article
(This article belongs to the Special Issue Secondary Metabolism of Microorganisms 2.0)
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16 pages, 2194 KiB  
Review
The Potential Use of Fungal Co-Culture Strategy for Discovery of New Secondary Metabolites
by Shuang Xu, Mengshi Li, Zhe Hu, Yilan Shao, Jialiang Ying and Huawei Zhang
Microorganisms 2023, 11(2), 464; https://doi.org/10.3390/microorganisms11020464 - 12 Feb 2023
Cited by 6 | Viewed by 3308
Abstract
Fungi are an important and prolific source of secondary metabolites (SMs) with diverse chemical structures and a wide array of biological properties. In the past two decades, however, the number of new fungal SMs by traditional monoculture method had been greatly decreasing. Fortunately, [...] Read more.
Fungi are an important and prolific source of secondary metabolites (SMs) with diverse chemical structures and a wide array of biological properties. In the past two decades, however, the number of new fungal SMs by traditional monoculture method had been greatly decreasing. Fortunately, a growing number of studies have shown that co-culture strategy is an effective approach to awakening silent SM biosynthetic gene clusters (BGCs) in fungal strains to produce cryptic SMs. To enrich our knowledge of this approach and better exploit fungal biosynthetic potential for new drug discovery, this review comprehensively summarizes all fungal co-culture methods and their derived new SMs as well as bioactivities on the basis of an extensive literature search and data analysis. Future perspective on fungal co-culture study, as well as its interaction mechanism, is supplied. Full article
(This article belongs to the Special Issue Secondary Metabolism of Microorganisms 2.0)
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43 pages, 1491 KiB  
Review
Sustainable Applications of Endophytic Bacteria and Their Physiological/Biochemical Roles on Medicinal and Herbal Plants: Review
by Phumudzo Patrick Tshikhudo, Khayalethu Ntushelo and Fhatuwani Nixwell Mudau
Microorganisms 2023, 11(2), 453; https://doi.org/10.3390/microorganisms11020453 - 10 Feb 2023
Cited by 6 | Viewed by 3168
Abstract
Bacterial endophytes reside within the tissues of living plant species without causing any harm or disease to their hosts. These endophytes can be isolated, identified, characterized, and used as biofertilizers. Moreover, bacterial endophytes increase the plants’ resistance against diseases, pests, and parasites, and [...] Read more.
Bacterial endophytes reside within the tissues of living plant species without causing any harm or disease to their hosts. These endophytes can be isolated, identified, characterized, and used as biofertilizers. Moreover, bacterial endophytes increase the plants’ resistance against diseases, pests, and parasites, and are a promising source of pharmaceutically important bioactives. For instance, the production of antibiotics, auxins, biosurfactants, cytokinin’s, ethylene, enzymes, gibberellins, nitric oxide organic acids, osmolytes, and siderophores is accredited to the existence of various bacterial strains. Thus, this manuscript intends to review the sustainable applications of endophytic bacteria to promote the growth, development, and chemical integrity of medicinal and herbal plants, as well as their role in plant physiology. The study of the importance of bacterial endophytes in the suppression of diseases in medicinal and herbal plants is crucial and a promising area of future investigation. Full article
(This article belongs to the Special Issue Secondary Metabolism of Microorganisms 2.0)
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