ABSTRACT
Secondary metabolites produced by fungi are well known for their biological properties, which play important roles in medicine. These metabolites aid in managing infections and treating chronic illnesses, thereby contributing substantially to human health improvement. Despite this extensive knowledge, the vast biodiversity and biosynthetic potential of fungi is still largely unexplored, highlighting the need for further research in natural products. In this review, several secondary metabolites of fungal origin are described, emphasizing novel structures and skeletons. The detection and characterization of these metabolites have been significantly facilitated by advancements in analytical systems, particularly modern hyphenated liquid chromatography/mass spectrometry. These improvements have primarily enhanced sensitivity, resolution, and analysis flow velocity. Since the in vitro production of novel metabolites is often lower than the re-isolation of known metabolites, understanding chromatin-based alterations in fungal gene expression can elucidate potential pathways for discovering new metabolites. Several protocols for inducing metabolite production from different strains are discussed, demonstrating the need for uniformity in experimental procedures to achieve consistent biosynthetic activation.
Subject(s)
Biological Products , Chromatin , Fungi , Fungi/metabolism , Chromatin/metabolism , Biological Products/metabolism , Secondary Metabolism , HumansABSTRACT
Four new polyketides, namely furantides A-B (1-2), talamin E (3) and arugosinacid A (4), and two known polyketides were obtained from the mangrove-derived fungus Penicillium sp. HDN15-312 using the One Strain Many Compounds (OSMAC) strategy. Their chemical structures, including configurations, were elucidated by detailed analysis of extensive NMR spectra, HRESIMS and ECD. The DPPH radicals scavenging activity of 3, with an IC50 value of 6.79 µM, was better than vitamin C.
Subject(s)
Penicillium , Polyketides , Penicillium/chemistry , Polyketides/pharmacology , Polyketides/chemistry , Polyketides/isolation & purification , Free Radical Scavengers/pharmacology , Free Radical Scavengers/chemistry , Free Radical Scavengers/isolation & purification , Magnetic Resonance Spectroscopy , Molecular Structure , Picrates , Rhizophoraceae/microbiology , Biphenyl CompoundsABSTRACT
The fungus Phialomyces macrosporus was cultured using the One Strain Many Compounds (OSMAC) strategies to evaluate its metabolome. Variations in the nutrient culture media, culture regime, and cultivation parameters can significantly influence fungal extract quantity and chemical diversity. This study aimed to explore the mycobolome of P. macrosporus in five different culture media and two different cultivation conditions using NMR-based metabolomics. Principal component analysis (PCA) of 1H NMR spectra revealed clear differentiation between these samples, highlighting the rice dextrose agar medium (RDA) and potato dextrose broth (PDB) as standard complex media for conducting a fungal metabolite screening program.
ABSTRACT
Genome mining in association with the OSMAC (one strain, many compounds) approach provides a feasible strategy to extend the chemical diversity and novelty of natural products. In this study, we identified the biosynthetic gene cluster (BGC) of restricticin, a promising antifungal agent featuring a reactive primary amine, from the fungus Aspergillus sclerotiorum LZDX-33-4 by genome mining. Combining heterologous expression and the OSMAC strategy resulted in the production of a new hybrid product (1), along with N-acetyl-restricticin (2) and restricticinol (3). The structure of 1 was determined by spectroscopic data, including optical rotation and electronic circular dichroism (ECD) calculations, for configurational assignment. Compound 1 represents a fusion of restricticin and phytotoxic cichorin. The biosynthetic pathway of 1 was proposed, in which the condensation of a primary amine of restricticin with a precursor of cichorine was postulated. Compound 1 at 5 mM concentration inhibited the growth of the shoots and roots of Lolium perenne, Festuca arundinacea, and Lactuca sativa with inhibitory rates of 71.3 and 88.7% for L. perenne, 79.4 and 73.0% for F. arundinacea, and 58.2 and 52.9% for L. sativa. In addition, compound 1 at 25 µg/mL showed moderate antifungal activity against Fusarium fujikuroi and Trichoderma harzianum with inhibition rates of 22.6 and 31.6%, respectively. These results suggest that heterologous expression in conjunction with the OSMAC approach provides a promising strategy to extend the metabolite novelty due to the incorporation of endogenous metabolites from the host strain with exogenous compounds, leading to the production of more complex compounds and the acquisition of new physiological functions.
Subject(s)
Lactuca , Lolium , Lolium/genetics , Lolium/drug effects , Lolium/growth & development , Lolium/metabolism , Lactuca/drug effects , Lactuca/genetics , Lactuca/growth & development , Multigene Family , Festuca/genetics , Festuca/metabolism , Festuca/microbiology , Festuca/drug effects , Festuca/growth & development , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemistry , Fungicides, Industrial/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Fungal Proteins/chemistry , Biosynthetic Pathways , Plant Roots/genetics , Plant Roots/metabolism , Plant Roots/growth & development , Plant Roots/drug effects , Plant Roots/microbiology , Molecular Structure , Genome, Fungal , Ascomycota/genetics , Ascomycota/drug effects , Ascomycota/metabolism , Fusarium/drug effects , Fusarium/genetics , Fusarium/growth & developmentABSTRACT
The fungus Talaromyces hainanensis, isolated from the mangrove soil, was characterized as a novel species by morphology observation and phylogenetic analyses. Four new γ-lactam alkaloids talaroilactams A-D (1-4) and two reported compounds harzianic acid (5) and isoharzianic acid (6) were identified from the fungus T. hainanensis WHUF0341, assisted by OSMAC along with molecular networking approaches. Their structures were determined through ECD calculations and spectroscopic analyses. Moreover, the biosynthetic route of 1-4 was also proposed. Compound 1 displayed potent cytotoxicity against HepG2 cell lines, with an IC50 value of 10.75 ± 1.11 µM. In addition, network pharmacology was employed to dissect the probable mechanisms contributing to the antihepatocellular carcinoma effects of compound 1, revealing that cytotoxicity was mainly associated with proteolysis, negative regulation of autophagy, inflammatory response, and the renin-angiotensin system. These results not only expanded the chemical space of natural products from the mangrove associated fungi but also afforded promising lead compounds for developing the antihepatocellular carcinoma agents.
Subject(s)
Alkaloids , Antineoplastic Agents , Lactams , Talaromyces , Talaromyces/chemistry , Talaromyces/metabolism , Humans , Alkaloids/pharmacology , Alkaloids/chemistry , Hep G2 Cells , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Lactams/chemistry , Lactams/pharmacology , Phylogeny , Molecular Structure , Wetlands , Rhizophoraceae/microbiology , Rhizophoraceae/chemistryABSTRACT
Fungi possess well-developed secondary metabolism pathways that are worthy of in-depth exploration. The One Strain Many Compounds (OSMAC) strategy is a useful method for exploring chemically diverse secondary metabolites. In this study, continued chemical investigations of the marine red algae-derived endophytic fungus Penicillium oxalicum 2021CDF-3 cultured in PDB media yielded six structurally diverse indole derivatives, including two new prenylated indole alkaloids asperinamide B (1) and peniochroloid B (5), as well as four related derivatives (compounds 2-4 and 6). The chemical structures of these compounds, including the absolute configurations of 1 and 5, were determined by extensive analyses of HRESIMS, 1D and 2D NMR spectroscopic data, and TDDFT-ECD calculations. Compound 1 was found to possess an unusual 3-pyrrolidone dimethylbenzopyran fused to the bicyclo[2.2.2]diazaoctane moiety, which was rare in previously reported prenylated indole alkaloids. In vitro cytotoxic experiments against four human tumor cell lines (HeLa, HepG2, FADU, and A549) indicated that 1 strongly inhibited the FADU cell line, with an IC50 value of 0.43 ± 0.03 µM. This study suggested that the new prenylated indole alkaloid 1 is a potential lead compound for anti-FADU drugs.
ABSTRACT
Four extracts of the marine-derived fungus Penicillium velutinum J.F.H. Beyma were obtained via metal ions stress conditions based on the OSMAC (One Strain Many Compounds) strategy. Using a combination of modern approaches such as LC/UV, LC/MS and bioactivity data analysis, as well as in silico calculations, influence metal stress factors to change metabolite profiles Penicillium velutinum were analyzed. From the ethyl acetate extract of the P. velutinum were isolated two new piperazine derivatives helvamides B (1) and C (2) together with known saroclazin A (3) (4S,5R,7S)-4,11-dihydroxy-guaia-1(2),9(10)-dien (4). Their structures were established based on spectroscopic methods. The absolute configuration of helvamide B (1) as 2R,5R was determined by a combination of the X-ray analysis and by time-dependent density functional theory (TD-DFT) calculations of electronic circular dichroism (ECD) spectra. The cytotoxic activity of the isolated compounds against human prostate cancer PC-3 and human embryonic kidney HEK-293 cells and growth inhibition activity against yeast-like fungi Candida albicans were assayed.
ABSTRACT
OSMAC strategy is a useful tool for discovering series of metabolites from microorganism. Five new sambutoxin derivatives (1-2, 4, 8-9), together with seven known compounds (3, 5-7, 10-12), were isolated from Talaromyces sp. CY-3 under OSMAC strategy and guidance of molecular networking. Their planar structures and absolute configurations were determined by NMR, HRESIMS, ECD spectra and common biosynthetic pathway. In bioassay, compounds 1-12 showed cytotoxicity to tumor cell lines with IC50 values in the range of 1.76-49.13 µM. The antitumor molecular mechanism of 10 was also explored. In vitro compound 10 significantly inhibited the growth and proliferation of two lung cancer cell lines (A549 and H1703). Furthermore, colony formation, EdU analysis, flow cytometry and Western blot analysis showed that 10 could induce cell cycle arrest in G0/G1 phase by promoting the expression of p53 and p21. The molecular mechanism of its antitumor effects in vitro is that 10 arrests the cell cycle by activating the p21/CyclinD1/Rb signaling pathway and the p53 pathway. Our results identified a lead small molecule compound with efficient antitumor growth and proliferation activity.
Subject(s)
Antineoplastic Agents , Pyridines , Talaromyces , Talaromyces/chemistry , Antineoplastic Agents/chemistry , Tumor Suppressor Protein p53 , Cell Line, Tumor , Molecular StructureABSTRACT
The OSMAC (one strain many compounds) concept is a cultivation-based approach to increase the diversity of secondary metabolites in microorganisms. In this study, we applied the OSMAC-approach to the endophytic fungus Trichocladium sp. by supplementation of the cultivation medium with 2.5% phenylalanine. This experiment yielded five new compounds, trichocladiol (1), trichocladic acid (2), colletodiolic acid (3), colletolactone (4) and colletolic acid (5), together with five previously described ones (6-10). The structures were elucidated via comprehensive spectroscopic measurements, and the absolute configurations of compound 1 was elucidated by using TDDFT-ECD calculations. For formation of compounds 3-5, a pathway based on colletodiol biosynthesis is proposed. Compound 6 exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus with a minimal inhibitory concentration (MIC) of 0.78 µM as well as a strong cytotoxic effect against the human monocytic cell line THP1 with an IC50 of 0.7 µM. Compound 8 showed moderate antibacterial activity against Mycobacterium tuberculosis with a MIC of 25 µM and a weak cytotoxic effect against THP1 cells with an IC50 of 42 µM.
Subject(s)
Anti-Bacterial Agents , Endophytes , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Mycobacterium tuberculosis , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/chemistry , Molecular Structure , Methicillin-Resistant Staphylococcus aureus/drug effects , Mycobacterium tuberculosis/drug effects , Endophytes/chemistry , Hypocreales/chemistry , THP-1 Cells , ChinaABSTRACT
Eight new 12,8-eudesmanolide sesquiterpenes, eutypellaolides A-H (1-8), and two new eudesmane-type sesquiterpenes, eutypellaolides I-J (9-10), along with four known 12,8-eudesmanolide compounds 11-14, were isolated from the culture extract of the polar fungus Eutypella sp. D-1 by one strain many compounds (OSMAC) approach. The structures of these compounds were determined through comprehensive spectroscopic data and experimental and calculated ECD analysis. Antibacterial, immunosuppressive, and PTP1B inhibition activities of these compounds were evaluated. Compounds 1 and 11 exhibited strong inhibitory activities against Bacillus subtilis and Staphylococcus aureus, with each showing an MIC value of 2 µg/mL. Compound 9 displayed weak immunosuppressive activity against ConA-induced T-cell proliferation with an inhibitory rate of 61.7% at a concentration of 19.8 µM. Compounds 5, 11, and 14 exhibited weak PTP1B inhibition activities with IC50 values of 44.8, 43.2, and 49.5 µM, respectively.
ABSTRACT
Co-cultivation, coupled with the OSMAC approach, is considered an efficient method for expanding microbial chemical diversity through the activation of cryptic biosynthetic gene clusters (BGCs). As part of our project aiming to discover new fungal metabolites for crop protection, we previously reported five polyketides, the macrolides dendrodolides E (1) and N (2), the azaphilones spiciferinone (3) and 8α-hydroxy-spiciferinone (4), and the bis-naphtho-γ-pyrone cephalochromin (5) from the solid Potato Dextrose Agar (PDA) co-culture of two marine sediment-derived fungi, Plenodomus influorescens and Pyrenochaeta nobilis. However, some of the purified metabolites could not be tested due to their minute quantities. Here we cultivated these fungi (both axenic and co-cultures) in liquid regime using three different media, Potato Dextrose Broth (PDB), Sabouraud Dextrose Broth (SDB), and Czapek-Dox Broth (CDB), with or without shaking. The aim was to determine the most ideal co-cultivation conditions to enhance the titers of the previously isolated compounds and to produce extracts with stronger anti-phytopathogenic activity as a basis for future upscaled fermentation. Comparative metabolomics by UPLC-MS/MS-based molecular networking and manual dereplication was employed for chemical profiling and compound annotations. Liquid co-cultivation in PDB under shaking led to the strongest activity against the phytopathogen Phytophthora infestans. Except for compound 1, all target compounds were detected in the co-culture in PDB. Compounds 2 and 5 were produced in lower titers, whereas the azaphilones (3 and 4) were overexpressed in PDB compared to PDA. Notably, liquid PDB co-cultures contained meroterpenoids and depside clusters that were absent in the solid PDA co-cultures. This study demonstrates the importance of culture regime in BGC regulation and chemical diversity of fungal strains in co-culture studies.
Subject(s)
Metabolome , Tandem Mass Spectrometry , Coculture Techniques , Chromatography, Liquid , Culture Media , GlucoseABSTRACT
Microbial secondary metabolites are pivotal for the development of novel drugs. However, conventional culture techniques, have left a vast array of unexpressed biosynthetic gene clusters (BGCs) in microorganisms, hindering the discovery of metabolites with distinct structural features and diverse biological functions. To address this limitation, several innovative strategies have been emerged. The "One Strain Many Compounds" (OSMAC) strategy, which involves altering microbial culture conditions, has proven to be particularly effective in mining numerous novel secondary metabolites for the past few years. Among these, microbial cyclic peptides stand out. These peptides often comprise rare amino acids, unique chemical structures, and remarkable biological function. With the advancement of the OSMAC strategy, a plethora of new cyclic peptides have been identified from diverse microbial genera. This work reviews the progress in mining novel compounds using the OSMAC strategy and the applications of this strategy in discovering 284 microbial cyclic peptides from 63 endophytic strains, aiming to offer insights for the further explorations into novel active cyclic peptides.
Subject(s)
Multigene Family , Peptides, Cyclic , Peptides, Cyclic/pharmacology , Secondary Metabolism/geneticsABSTRACT
Fungi are microorganisms of significant biotechnological importance due to their ability to provide food and produce several value-added secondary metabolites and enzymes. Its products move billions of dollars in the pharmaceutical, cosmetics, and additives sectors. These microorganisms also play a notable role in bionanotechnology, leading to the production of hybrid biological-inorganic materials (such as cyborg cells) and the use of their enzyme complex in the biosynthesis of nanoparticles. In this sense, optimizing the fungal growth process is necessary, with selecting the cultivation medium as one of the essential factors for the microorganism to reach its maximum metabolic expression. The culture medium's composition can also impact the nanomaterial's stability and prevent the incorporation of nanoparticles into fungal cells. Therefore, our main objectives are the following: (1) compile and discuss the most commonly employed culture media for the production of fungal secondary metabolites and the formation of cyborg cells, accompanied by preparation methods; (2) provide a six-step guide to investigating the fungal metabolomic profile and (3) discuss the main procedures of microbial cultivation to produce fungal cyborg cells.
Subject(s)
Fungi , Metabolomics , Metabolomics/methods , Culture Media , Fungi/metabolismABSTRACT
Unsaturated diacylglycerols are a class of antioxidant compounds with the potential to positively impact human health. Their ability to combat oxidative stress through radical scavenger activity underscores their significance in the context of preventive and therapeutic strategies. In this paper we highlight the role of Anabaena flos-aquae as a producer of unsaturated mono and diacylglycerols, and then demonstrate the antioxidant activity of its methanolic extract, which has as its main components a variety of acylglycerol analogues. This finding was revealed using a sustainable strategy in which the One Strain Many Compounds (OSMAC) cultivation in microscale was coupled with a bioinformatic approach to analyze a large dataset of mass spectrometry data using the molecular networking analyses. This strategy reduces time and costs, avoiding long and expensive steps of purification and obtaining informative data on the metabolic composition of the extracts. This study highlights the role of Anabaena as a sustainable and green source of novel bioactive compounds.
ABSTRACT
Based on the One Strain-Many Compounds (OSMAC) strategy, the secondary metabolites of Phomopsis lithocarpus FS508 were investigated. As a result, a new secondary metabolite, 4-methoxy-3-[4-(acetyloxy)-3-methyl-2-butenyl]benzoic acid (1) as well as eleven known compounds were isolated from the fermentation product of the strain FS508. Their structures were determined by NMR, IR, UV, and MS spectroscopic data analyses. All the isolated compounds were evaluated for cytotoxic and anti-inflammatory activities. Among them, compounds 3 and 9 displayed potent cytotoxicity against HepG-2 cell line, and compounds 2, 3 and 12 showed significant anti-inflammatory activities.
Subject(s)
Antineoplastic Agents , Ascomycota , Phomopsis , Ascomycota/chemistry , Cell Line, Tumor , Antineoplastic Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Molecular StructureABSTRACT
Mangrove-derived fungi have been demonstrated to be promising source of structurally diverse and widely active secondary metabolites. During our search for new bioactive compounds, eight new indole-benzodiazepine-2,5-dione derivatives asperdinones A-H (1-8) and two known congeners (9 and 10) were isolated from the culture extracts of the mangrove-derived fungus Aspergillus spinosus WHUF0344 guided by one strain many compounds (OSMAC) and the heteronuclear 1H, 13C single-quantum coherence (HSQC) based small molecule accurate recognition technology (SMART) strategies. The structures and absolute configurations of the new compounds were elucidated by detailed spectroscopic analyze and electronic circular dichroism (ECD) calculations. The putative biosynthetic pathway of these compounds was proposed. Compounds 1-10 were evaluated for their antibacterial and α-glucosidase inhibitory activities. None of compounds showed antibacterial activity. Compounds 2-6 and 8 exhibited moderate inhibitory effects against α-glucosidase with IC50 values in the range of 24.65-312.25 µM. Besides, both 3 and 4 inhibited α-glucosidase variedly. Furthermore, the molecular docking study showed that compounds 2-4 were perfectly docking into the active sites of α-glucosidase. This study not only enriched the chemical diversity of secondary metabolites from the mangrove-derived fungi, but also provided potential hit compounds for further development of α-glucosidase inhibitors.
Subject(s)
Aspergillus , Benzodiazepines , alpha-Glucosidases , alpha-Glucosidases/metabolism , Molecular Docking Simulation , Fungi/metabolism , Circular Dichroism , Indoles , Glycoside Hydrolase Inhibitors/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Molecular StructureABSTRACT
The fungal strain BC17 was isolated from sediments collected in the intertidal zone of the inner Bay of Cadiz and characterized as Emericellopsis maritima. On the basis of the one strain-many compounds (OSMAC) approach, four new eremophilane-type sesquiterpenes (1-4), together with thirteen known derivatives (5-17) and two reported diketopiperazines (18, 19), were isolated from this strain. The chemical structures and absolute configurations of the new compounds were determined through extensive NMR and HRESIMS spectroscopic studies and ECD calculation. Thirteen of the isolated eremophilanes were examined for cytotoxic and antimicrobial activities. PR toxin (16) exhibited cytotoxic activity against HepG2, MCF-7, A549, A2058, and Mia PaCa-2 human cancer cell lines with IC50 values ranging from 3.75 to 33.44 µM. (+)-Aristolochene (10) exhibited selective activity against the fungal strains Aspergillus fumigatus ATCC46645 and Candida albicans ATCC64124 at 471 µM.
Subject(s)
Anti-Infective Agents , Antineoplastic Agents , Hypocreales , Sesquiterpenes , Humans , Polycyclic Sesquiterpenes , Sesquiterpenes/chemistry , Antineoplastic Agents/chemistry , Geologic Sediments/microbiology , Anti-Infective Agents/chemistry , Molecular StructureABSTRACT
The secondary metabolites of marine fungi with rich chemical diversity and biological activity are an important and exciting target for natural product research. This study aimed to investigate the fungal community in Quanzhou Bay, Fujian, and identified 28 strains of marine fungi. A total of 28 strains of marine fungi were screened for small-scale fermentation by the OSMAC (One Strain-Many Compounds) strategy, and 77 EtOAc crude extracts were obtained and assayed for cancer cell inhibition rate. A total of six strains of marine fungi (P-WZ-2, P-WZ-3-2, P-WZ-4, P-WZ-5, P56, and P341) with significant changes in cancer cell inhibition induced by the OSMAC strategy were analysed by UPLC-QTOF-MS. The ACD/MS Structure ID Suite software was used to predict the possible structures with inhibitory effects on cancer cells. A total of 23 compounds were identified, of which 10 compounds have been reported to have potential anticancer activity or cytotoxicity. In this study, the OSMAC strategy was combined with an untargeted metabolomics approach based on UPLC-QTOF-MS to efficiently analyse the effect of changes in culture conditions on anticancer potentials and to rapidly find active substances that inhibit cancer cell growth.
Subject(s)
Fungi , Metabolomics , Chromatography, High Pressure Liquid , Fungi/metabolism , FermentationABSTRACT
Introduction: Alkaloidal natural products are attractive for their broad spectrum of pharmaceutical bioactivities. In the present work, the highly productive saline soil derived fungus, Penicillium raistrichii, was subjected to the strategy of OSMAC (one strain many compounds) with changes of cultivation status. Then, the work-flow led to the expansion of the alkaloid chemical diversity and subsequently induced the accumulation of four undescribed alkaloids, named raistrimides A-D (1-4), including three ß-carbolines (1-3), one 2-quinolinone (4), and one new natural product, 2-quinolinone (5), along with five known alkaloid chemicals (6-10). Methods: A set of NMR techniques including 1H, 13C, HSQC and HMBC, along with other spectroscopic data of UV-Vis, IR and HRESIMS, were introduced to assign the plain structures of compounds 1-10. The absolute configuration of 1-3 were elucidated by means of X-ray crystallography or spectroscopic analyses on optical rotation values and experimental electronic circular dichroism (ECD) data. In addition, it was the first report on the confirmation of structures of 6, 7 and 9 by X-ray crystallography data. The micro-broth dilution method was applied to evaluate antimicrobial effect of all compounds towards Staphylococcus aureus, Escherichia coli, and Candida albicans. Results and discussion: The results indicated compounds 1, 3 and 4 to be bioactive, which may be potential for further development of anti-antimicrobial agents. The finding in this work implied that OSMAC strategy was a powerful and effective tool for promotion of new chemical entities from P. raistrichii.
ABSTRACT
Using the OSMAC (One Strain Many Compounds) approach, the actinobacterium Streptomyces griseorubiginosus, derived from an unidentified cnidarian collected from a reef near Pointe de Bellevue in Réunion Island (France), was subjected to cultivation under diverse conditions. This endeavour yielded the isolation of a repertoire of 23 secondary metabolites (1-23), wherein five compounds were unprecedented as natural products (19-23). Specifically, compounds 19 and 20 showcased novel anthrone backbones, while compound 23 displayed a distinctive tetralone structure. Additionally, compounds 21 and 22 presented an unusual naphtho [2,3-c]furan-4(9H)-one chromophore. Interestingly, the detection of all these novel compounds (19-23) was exclusively achieved when the bacterium was cultured in FA-1 liquid medium supplemented with the epigenetic modifier γ-butyrolactone. The elucidation of the structural features of the newfound compounds was accomplished through a combination of HRESIMS, 1D and 2D NMR spectroscopy, as well as QM-NMR (Quantum Mechanical-Nuclear Magnetic Resonance) methods and by comparison with existing literature. Moreover, the determination of the relative configuration of compound 23 was facilitated by employing the mix-J-DP4 computational approach.