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21 pages, 4309 KiB

Open AccessArticle

A Neutral Polysaccharide from Spores of Ophiocordyceps gracilis Regulates Oxidative Stress via NRF2/FNIP1 Pathway

by Yue Wang, Shixiang Wei, Hui Lian, Lingling Tong, Linhui Yang, Bo Ren, Dongsheng Guo and He Huang

Int. J. Mol. Sci. 2023, 24(19), 14721; https://doi.org/10.3390/ijms241914721 - 29 Sep 2023

Cited by 6 | Viewed by 1425

Abstract

Ophiocordyceps gracilis (O. gracilis) is a parasitic fungus used in traditional Chinese medicine and functional foods. In this study, a neutral heteropolysaccharide (GSP-1a) was isolated from spores of O. gracilis, and its structure and antioxidant capacities were investigated. GSP-1a was [...] Read more.

Ophiocordyceps gracilis (O. gracilis) is a parasitic fungus used in traditional Chinese medicine and functional foods. In this study, a neutral heteropolysaccharide (GSP-1a) was isolated from spores of O. gracilis, and its structure and antioxidant capacities were investigated. GSP-1a was found to have a molecular weight of 72.8 kDa and primarily consisted of mannose (42.28%), galactose (35.7%), and glucose (22.02%). The backbone of GSP-1a was composed of various sugar residues, including →6)-α-D-Manp-(1→, →2,6)-α-D-Manp-(1→, →2,4,6)-α-D-Manp-(1→, →6)-α-D-Glcp-(1→, and →3,6)-α-D-Glcp-(1→, with some branches consisting of →6)-α-D-Manp-(1→ and α-D-Gal-(1→. In vitro, antioxidant activity assays demonstrated that GSP-1a exhibited scavenging effects on hydroxyl radical (^•OH), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical cation (ABTS^•+), and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH^•). Moreover, GSP-1a was found to alleviate H₂O₂-induced oxidative stress in HepG2 cells by reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while enhancing the activities of superoxide dismutase (SOD). Furthermore, GSP-1a upregulated the mRNA expression of antioxidant enzymes such as Ho-1, Gclm, and Nqo1, and regulated the NRF2/KEAP1 and FNIP1/FEM1B pathways. The findings elucidated the structural types of GSP-1a and provided a reliable theoretical basis for its usage as a natural antioxidant in functional foods or medicine. Full article

(This article belongs to the Special Issue Bioactive Natural Products: Isolation, Structural Elucidation and Biological Assays)

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20 pages, 4531 KiB

Open AccessArticle

Stereomeric Lipopeptides from a Single Non-Ribosomal Peptide Synthetase as an Additional Source of Structural and Functional Diversification in Pseudomonas Lipopeptide Biosynthesis

by Penthip Muangkaew, Vic De Roo, Lu Zhou, Léa Girard, Catherine Cesa-Luna, Monica Höfte, René De Mot, Annemieke Madder, Niels Geudens and José C. Martins

Int. J. Mol. Sci. 2023, 24(18), 14302; https://doi.org/10.3390/ijms241814302 - 19 Sep 2023

Cited by 4 | Viewed by 2021

Abstract

In Pseudomonas lipopeptides, the D-configuration of amino acids is generated by dedicated, dual-function epimerization/condensation (E/C) domains. The increasing attention to stereochemistry in lipopeptide structure elucidation efforts has revealed multiple examples where epimerization does not occur, even though an E/C-type domain is present. While [...] Read more.

In Pseudomonas lipopeptides, the D-configuration of amino acids is generated by dedicated, dual-function epimerization/condensation (E/C) domains. The increasing attention to stereochemistry in lipopeptide structure elucidation efforts has revealed multiple examples where epimerization does not occur, even though an E/C-type domain is present. While the origin of the idle epimerization in those E/C-domains remains elusive, epimerization activity has so far shown a binary profile: it is either ‘on’ (active) or ‘off’ (inactive). Here, we report the unprecedented observation of an E/C-domain that acts ‘on and off’, giving rise to the production of two diastereoisomeric lipopeptides by a single non-ribosomal peptide synthetase system. Using dereplication based on solid-phase peptide synthesis and NMR fingerprinting, we first show that the two cyclic lipopeptides produced by Pseudomonas entomophila COR5 correspond to entolysin A and B originally described for P. entomophila L48. Next, we prove that both are diastereoisomeric homologues differing only in the configuration of a single amino acid. This configurational variability is maintained in multiple Pseudomonas strains and typically occurs in a 3:2 ratio. Bioinformatic analysis reveals a possible correlation with the composition of the flanking sequence of the N-terminal secondary histidine motif characteristic for dual-function E/C-type domains. In permeabilization assays, using propidium iodide entolysin B has a higher antifungal activity compared to entolysin A against Botrytis cinerea and Pyricularia oryzae spores. The fact that configurational homologues are produced by the same NRPS system in a Pseudomonas strain adds a new level of structural and functional diversification to those already known from substrate flexibility during the recruitment of the amino acids and fatty acids and underscores the importance of complete stereochemical elucidation of non-ribosomal lipopeptide structures. Full article

(This article belongs to the Special Issue Bioactive Natural Products: Isolation, Structural Elucidation and Biological Assays)

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9 pages, 2044 KiB

Open AccessArticle

Eupatin, a Flavonoid, Inhibits Coronavirus 3CL Protease and Replication

by Yea-In Park, Jang Hoon Kim, Siyun Lee, Ik Soo Lee and Junsoo Park

Int. J. Mol. Sci. 2023, 24(11), 9211; https://doi.org/10.3390/ijms24119211 - 24 May 2023

Cited by 4 | Viewed by 1714

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has caused more than six million deaths worldwide since 2019. Although vaccines are available, novel variants of coronavirus are expected to appear continuously, and there is a need for a more effective remedy for coronavirus disease. In [...] Read more.

The coronavirus disease 2019 (COVID-19) pandemic has caused more than six million deaths worldwide since 2019. Although vaccines are available, novel variants of coronavirus are expected to appear continuously, and there is a need for a more effective remedy for coronavirus disease. In this report, we isolated eupatin from Inula japonica flowers and showed that it inhibits the coronavirus 3 chymotrypsin-like (3CL) protease as well as viral replication. We showed that eupatin treatment inhibits SARS-CoV-2 3CL-protease, and computational modeling demonstrated that it interacts with key residues of 3CL-protease. Further, the treatment decreased the number of plaques formed by human coronavirus OC43 (HCoV-OC43) infection and decreased viral protein and RNA levels in the media. These results indicate that eupatin inhibits coronavirus replication. Full article

(This article belongs to the Special Issue Bioactive Natural Products: Isolation, Structural Elucidation and Biological Assays)

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13 pages, 2257 KiB

Open AccessArticle

(±)-3-Deoxyradicinin Induces Stomata Opening and Chloroplast Oxidative Stress in Tomato (Solanum lycopersicum L.)

by Simone Samperna, Clarissa Zanotti, Patrizia Scafato, Angela Boari, Sabina Visconti, Maurizio Vurro, Stefano Superchi, Antonio Evidente and Mauro Marra

Int. J. Mol. Sci. 2023, 24(10), 8467; https://doi.org/10.3390/ijms24108467 - 9 May 2023

Cited by 3 | Viewed by 1449

Abstract

Radicinin is a phytotoxic dihydropyranopyran-4,5-dione isolated from the culture filtrates of Cochliobolus australiensis, a phytopathogenic fungus of the invasive weed buffelgrass (Cenchrus ciliaris). Radicinin proved to have interesting potential as a natural herbicide. Being interested in elucidating the mechanism of action [...] Read more.

Radicinin is a phytotoxic dihydropyranopyran-4,5-dione isolated from the culture filtrates of Cochliobolus australiensis, a phytopathogenic fungus of the invasive weed buffelgrass (Cenchrus ciliaris). Radicinin proved to have interesting potential as a natural herbicide. Being interested in elucidating the mechanism of action and considering radicinin is produced in small quantities by C. australiensis, we opted to use (±)-3-deoxyradicinin, a synthetic analogue of radicinin that is available in larger quantities and shows radicinin-like phytotoxic activities. To obtain information about subcellular targets and mechanism(s) of action of the toxin, the study was carried out by using tomato (Solanum lycopersicum L.), which, apart from its economic relevance, has become a model plant species for physiological and molecular studies. Results of biochemical assays showed that (±)-3-deoxyradicinin administration to leaves induced chlorosis, ion leakage, hydrogen peroxide production, and membrane lipid peroxidation. Remarkably, the compound determined the uncontrolled opening of stomata, which, in turn, resulted in plant wilting. Confocal microscopy analysis of protoplasts treated with (±)-3-deoxyradicinin ascertained that the toxin targeted chloroplasts, eliciting an overproduction of reactive singlet oxygen species. This oxidative stress status was related by qRT-PCR experiments to the activation of transcription of genes of a chloroplast-specific pathway of programmed cell death. Full article

(This article belongs to the Special Issue Bioactive Natural Products: Isolation, Structural Elucidation and Biological Assays)

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11 pages, 3735 KiB

Open AccessArticle

Identification of Novel Sphydrofuran-Derived Derivatives with Lipid-Lowering Activity from the Active Crude Extracts of Nocardiopsis sp. ZHD001

by Yuhong Tian, Yongjun Jiang, Zhengshun Wen, Liping Guan, Xiaokun Ouyang, Wanjing Ding and Zhongjun Ma

Int. J. Mol. Sci. 2023, 24(3), 2822; https://doi.org/10.3390/ijms24032822 - 1 Feb 2023

Cited by 7 | Viewed by 1993

Abstract

Lipid-lowering is one of the most effective methods of prevention and treatment for cardiovascular diseases. However, most clinical lipid-lowering drugs have adverse effects and cannot achieve the desired efficacy in some complex hyperlipidemia patients, so it is of great significance to develop safe [...] Read more.

Lipid-lowering is one of the most effective methods of prevention and treatment for cardiovascular diseases. However, most clinical lipid-lowering drugs have adverse effects and cannot achieve the desired efficacy in some complex hyperlipidemia patients, so it is of great significance to develop safe and effective novel lipid-lowering drugs. In the course of our project aimed at discovering the chemical novelty and bioactive natural products of marine-derived actinomycetes, we found that the organic crude extracts (OCEs) of Nocardiopsis sp. ZHD001 exhibited strong in vivo efficacies in reducing weight gain, lowering LDL-C, TC, and TG levels, and improving HDL-C levels in high-fat-diet-fed mice models. Chemical investigations of the active OCEs led to identifying two new sphydrofuran-derived compounds (1–2) and one known 2-methyl-4-(1-glycerol)-furan (3). Their structures were elucidated by the analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and ECD calculations. Among these compounds, compound 1 represents a novel rearranged sphydrofuran-derived derivative. Bioactivity evaluations of these pure compounds showed that all the compounds exhibited significant lipid-lowering activity with lower cytotoxicity in vitro compared to simvastatin. Our results demonstrate that sphydrofuran-derived derivatives might be promising candidates for lipid-lowering drugs. Full article

(This article belongs to the Special Issue Bioactive Natural Products: Isolation, Structural Elucidation and Biological Assays)

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18 pages, 5218 KiB

Open AccessArticle

Isolation, Identification, and Characterization of Bioactive Peptides in Human Bone Cells from Tortoiseshell and Deer Antler Gelatin

by Tsung-Jung Ho, Jung-Hsing Lin, Shinn Zong Lin, Wan-Ting Tsai, Jia-Ru Wu and Hao-Ping Chen

Int. J. Mol. Sci. 2023, 24(2), 1759; https://doi.org/10.3390/ijms24021759 - 16 Jan 2023

Cited by 3 | Viewed by 2515

Abstract

Tortoiseshell and deer antler gelatin has been used to treat bone diseases in Chinese society. A pepsin-digested gelatin peptide with osteoblast-proliferation-stimulating properties was identified via LC-MS/MS. The resulting pentapeptide, TSKYR, was presumably subjected to further degradation into TSKY, TSK, and YR fragments in [...] Read more.

Tortoiseshell and deer antler gelatin has been used to treat bone diseases in Chinese society. A pepsin-digested gelatin peptide with osteoblast-proliferation-stimulating properties was identified via LC-MS/MS. The resulting pentapeptide, TSKYR, was presumably subjected to further degradation into TSKY, TSK, and YR fragments in the small intestine. The above four peptides were chemically synthesized. Treatment of tripeptide TSK can lead to a significant 30- and 50-fold increase in the mineralized nodule area and density in osteoblast cells and a 47.5% increase in the number of chondrocyte cells. The calcium content in tortoiseshell was relatively higher than in human soft tissue. The synergistic effects of calcium ions and the peptides were observed for changes in osteoblast proliferation and differentiation. Moreover, these peptides can enhance the expression of RUNX2, OCN, FGFR2, and FRFR3 genes in osteoblasts, and aggrecan and collagen type II in chondrocyte (patent pending). Full article

(This article belongs to the Special Issue Bioactive Natural Products: Isolation, Structural Elucidation and Biological Assays)

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21 pages, 3348 KiB

Open AccessArticle

Characterization and Bioactive Potential of Secondary Metabolites Isolated from Piper sarmentosum Roxb.

by Ismail Ware, Katrin Franke, Mthandazo Dube, Hesham Ali El Enshasy and Ludger A. Wessjohann

Int. J. Mol. Sci. 2023, 24(2), 1328; https://doi.org/10.3390/ijms24021328 - 10 Jan 2023

Cited by 9 | Viewed by 3373

Abstract

Piper sarmentosum Roxb. (Piperaceae) is a traditional medicinal plant in South-East Asian countries. The chemical investigation of leaves from this species resulted in the isolation of three previously not described compounds, namely 4″-(3-hydroxy-3-methylglutaroyl)-2″-β-D-glucopyranosyl vitexin (1), kadukoside (2), [...] Read more.

Piper sarmentosum Roxb. (Piperaceae) is a traditional medicinal plant in South-East Asian countries. The chemical investigation of leaves from this species resulted in the isolation of three previously not described compounds, namely 4″-(3-hydroxy-3-methylglutaroyl)-2″-β-D-glucopyranosyl vitexin (1), kadukoside (2), and 6-O-trans-p-coumaroyl-D-glucono-1,4-lactone (3), together with 31 known compounds. Of these known compounds, 21 compounds were isolated for the first time from P. sarmentosum. The structures were established by 1D and 2D NMR techniques and HR-ESI-MS analyses. The compounds were evaluated for their anthelmintic (Caenorhabditis elegans), antifungal (Botrytis cinerea, Septoria tritici and Phytophthora infestans), antibacterial (Aliivibrio fischeri) and cytotoxic (PC-3 and HT-29 human cancer cells lines) activities. Methyl-3-(4-methoxyphenyl)propionate (8), isoasarone (12), and trans-asarone (15) demonstrated anthelmintic activity with IC₅₀ values between 0.9 and 2.04 mM. Kadukoside (2) was most active against S. tritici with IC₅₀ at 5.0 µM and also induced 94% inhibition of P. infestans growth at 125 µM. Trans-asarone (15), piperolactam A (23), and dehydroformouregine (24) displayed a dose-dependent effect against B. cinerea from 1.5 to 125 µM up to more than 80% inhibition. Paprazine (19), cepharadione A (21) and piperolactam A (23) inhibited bacterial growth by more than 85% at 100 µM. Only mild cytotoxic effects were observed. Full article

(This article belongs to the Special Issue Bioactive Natural Products: Isolation, Structural Elucidation and Biological Assays)

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13 pages, 1793 KiB

Open AccessArticle

Anti-Inflammatory Activity of Cajanin, an Isoflavonoid Derivative Isolated from Canavalia lineata Pods

by Su-Jin Hong, Ok-Kyoung Kwon, Daseul Hwang, Su Hyun Goo, Doo-Young Kim, Min Ha Kim, Soo-Young Kim, Hyun-Jae Jang and Sei-Ryang Oh

Int. J. Mol. Sci. 2022, 23(16), 9492; https://doi.org/10.3390/ijms23169492 - 22 Aug 2022

Cited by 5 | Viewed by 2316

Abstract

The bioactive components of Canavalia lineata (Thunb.) DC pods were investigated using bioactivity-guided isolation, and the chemical structures of flavonoids 1–3, isoflavonoid derivatives 4–11, and phenolic compounds 12 and 13 were identified by comparing NMR, MS, and [...] Read more.

The bioactive components of Canavalia lineata (Thunb.) DC pods were investigated using bioactivity-guided isolation, and the chemical structures of flavonoids 1–3, isoflavonoid derivatives 4–11, and phenolic compounds 12 and 13 were identified by comparing NMR, MS, and CD spectral data with previously reported spectroscopic data. Compounds 1–13 were evaluated for their anti-inflammatory effects on LPS-stimulated RAW264.7 macrophages. Among these compounds, the isoflavonoid derivative cajanin (7) exhibited the most potent anti-inflammatory activity (IC₅₀ of NO = 19.38 ± 0.05 µM; IC₅₀ of IL-6 = 7.78 ± 0.04 µM; IC₅₀ of TNF-α = 26.82 ± 0.11 µM), exerting its anti-inflammatory effects by suppressing the activation and nuclear translocation of the transcription factor NF-κB by phosphorylating IκB and p65. These results suggested that cajanin (7) may be a potential candidate for improving the treatment of inflammatory diseases. Full article

(This article belongs to the Special Issue Bioactive Natural Products: Isolation, Structural Elucidation and Biological Assays)

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12 pages, 981 KiB

Open AccessArticle

Antibiotic and Nematocidal Metabolites from Two Lichen Species Collected on the Island of Lampedusa (Sicily)

by Jesús García Zorrilla, Trifone D’Addabbo, Emanuela Roscetto, Chiara Varriale, Maria Rosaria Catania, Maria Chiara Zonno, Claudio Altomare, Giuseppe Surico, Pier Luigi Nimis and Antonio Evidente

Int. J. Mol. Sci. 2022, 23(15), 8471; https://doi.org/10.3390/ijms23158471 - 30 Jul 2022

Cited by 10 | Viewed by 2284

Abstract

The antibiotic and nematocidal activities of extracts from two coastal lichen species collected on Lampedusa Island (Sicily), Ramalina implexa Nyl. and Roccella phycopsis Ach., were tested. Methyl orsellinate, orcinol, (+)-montagnetol, and for the first time 4-chlororcinol were isolated from Roccella phycopsis. (+)-Usnic [...] Read more.

The antibiotic and nematocidal activities of extracts from two coastal lichen species collected on Lampedusa Island (Sicily), Ramalina implexa Nyl. and Roccella phycopsis Ach., were tested. Methyl orsellinate, orcinol, (+)-montagnetol, and for the first time 4-chlororcinol were isolated from Roccella phycopsis. (+)-Usnic acid was obtained from Ramalina implexa. The crude organic extract of both lichen species showed strong antibiotic activity against some bacterial species and nematocidal activity. Among all the pure metabolites tested against the infective juveniles (J2) of the root-knot nematode (RKN) Meloydogine incognita, (+)-usnic acid, orcinol, and (+)-montagnetol had significant nematocidal activity, comparable with that of the commercial nematocide Velum^® Prime, and thus they showed potential application in agriculture as a biopesticide. On the contrary, methyl orsellinate and 4-chlororcinol had no nematocidal effect. These results suggest that the substituent pattern at ortho-para-position in respect to both hydroxyl groups of resorcine moiety, which is present in all metabolites, seems very important for nematocidal activity. The organic extracts of both lichens were also tested against some Gram-positive and Gram-negative bacteria. Both extracts were active against Gram-positive species. The extract of Ramalina implexa showed, among Gram-negative species, activity against Escherichia coli and Acinetobacter baumannii, while that from Roccella phycopsis was effective towards all test strains, with the exception of Pseudomonas aeruginosa. The antimicrobial activity of (+)-usnic acid, methyl orsellinate, and (+)-montagnetol is already known, so tests were focused on orcinol and 4-chlororcinol. The former showed antibacterial activity against all Gram positive and Gram-negative test strains, with the exception of A. baumannii and K. pneumoniae, while the latter exhibited a potent antibacterial activity against Gram-positive test strains and among Gram-negative strains, was effective against A. baumannii and K. pneumonia. These results suggest, for orcinol and 4-chlororcinol, an interesting antibiotic potential against both Gram-positive and Gram-negative bacterial strains. Full article

(This article belongs to the Special Issue Bioactive Natural Products: Isolation, Structural Elucidation and Biological Assays)

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Review

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25 pages, 3266 KiB

Open AccessReview

Status of Phytotoxins Isolated from Necrotrophic Fungi Causing Diseases on Grain Legumes

by Francisco J. Agudo-Jurado, Pierluigi Reveglia, Diego Rubiales, Antonio Evidente and Eleonora Barilli

Int. J. Mol. Sci. 2023, 24(6), 5116; https://doi.org/10.3390/ijms24065116 - 7 Mar 2023

Cited by 5 | Viewed by 2347

Abstract

Fungal phytotoxins can be defined as secondary metabolites toxic to host plants and are believed to be involved in the symptoms developed of a number of plant diseases by targeting host cellular machineries or interfering with host immune responses. As any crop, legumes [...] Read more.

Fungal phytotoxins can be defined as secondary metabolites toxic to host plants and are believed to be involved in the symptoms developed of a number of plant diseases by targeting host cellular machineries or interfering with host immune responses. As any crop, legumes can be affected by a number of fungal diseases, causing severe yield losses worldwide. In this review, we report and discuss the isolation, chemical, and biological characterization of fungal phytotoxins produced by the most important necrotrophic fungi involved in legume diseases. Their possible role in plant–pathogen interaction and structure–toxicity relationship studies have also been reported and discussed. Moreover, multidisciplinary studies on other prominent biological activity conducted on reviewed phytotoxins are described. Finally, we explore the challenges in the identification of new fungal metabolites and their possible applications in future experiments. Full article

(This article belongs to the Special Issue Bioactive Natural Products: Isolation, Structural Elucidation and Biological Assays)

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34 pages, 14879 KiB

Open AccessReview

Bioactive Lipodepsipeptides Produced by Bacteria and Fungi

by Antonio Evidente

Int. J. Mol. Sci. 2022, 23(20), 12342; https://doi.org/10.3390/ijms232012342 - 15 Oct 2022

Cited by 9 | Viewed by 2946

Abstract

Natural products are a vital source for agriculture, medicine, cosmetics and other fields. Lipodepsipeptides (LPDs) are a wide group of natural products distributed among living organisms such as bacteria, fungi, yeasts, virus, insects, plants and marine organisms. They are a group of compounds [...] Read more.

Natural products are a vital source for agriculture, medicine, cosmetics and other fields. Lipodepsipeptides (LPDs) are a wide group of natural products distributed among living organisms such as bacteria, fungi, yeasts, virus, insects, plants and marine organisms. They are a group of compounds consisting of a lipid connected to a peptide, which are able to self-assemble into several different structures. They have shown different biological activities such as phytotoxic, antibiotic, antiviral, antiparasitic, antifungal, antibacterial, immunosuppressive, herbicidal, cytotoxic and hemolytic activities. Their biological activities seem to be due to their interactions with the plasma membrane (MP) because they are able to mimic the architecture of the native membranes interacting with their hydrophobic segment. LPDs also have surfactant properties. The review has been focused on the lipodepsipeptides isolated from fungal and bacterial sources, on their biological activity, on the structure–activity relationships of some selected LPD subgroups and on their potential application in agriculture and medicine. The chemical and biological characterization of lipodepsipeptides isolated in the last three decades and findings that resulted from SCI-FINDER research are reported. A critical evaluation of the most recent reviews dealing with the same argument has also been described. Full article

(This article belongs to the Special Issue Bioactive Natural Products: Isolation, Structural Elucidation and Biological Assays)

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25 pages, 9917 KiB

Open AccessReview

Novel Insights on Pyoverdine: From Biosynthesis to Biotechnological Application

by Filippo Dell’Anno, Giovanni Andrea Vitale, Carmine Buonocore, Laura Vitale, Fortunato Palma Esposito, Daniela Coppola, Gerardo Della Sala, Pietro Tedesco and Donatella de Pascale

Int. J. Mol. Sci. 2022, 23(19), 11507; https://doi.org/10.3390/ijms231911507 - 29 Sep 2022

Cited by 14 | Viewed by 4265

Abstract

Pyoverdines (PVDs) are a class of siderophores produced mostly by members of the genus Pseudomonas. Their primary function is to accumulate, mobilize, and transport iron necessary for cell metabolism. Moreover, PVDs also play a crucial role in microbes’ survival by mediating biofilm [...] Read more.

Pyoverdines (PVDs) are a class of siderophores produced mostly by members of the genus Pseudomonas. Their primary function is to accumulate, mobilize, and transport iron necessary for cell metabolism. Moreover, PVDs also play a crucial role in microbes’ survival by mediating biofilm formation and virulence. In this review, we reorganize the information produced in recent years regarding PVDs biosynthesis and pathogenic mechanisms, since PVDs are extremely valuable compounds. Additionally, we summarize the therapeutic applications deriving from the PVDs’ use and focus on their role as therapeutic target themselves. We assess the current biotechnological applications of different sectors and evaluate the state-of-the-art technology relating to the use of synthetic biology tools for pathway engineering. Finally, we review the most recent methods and techniques capable of identifying such molecules in complex matrices for drug-discovery purposes. Full article

(This article belongs to the Special Issue Bioactive Natural Products: Isolation, Structural Elucidation and Biological Assays)

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