# Revolutionizing microbial treasure troves: innovative strategies for natural products discovery

**Authors:** Yu-Jie Li, Ming-Hua Qiu, Xing-Rong Peng

PMC · DOI: 10.1007/s13659-025-00565-0 · Natural Products and Bioprospecting · 2026-01-10

## TL;DR

This review explores new methods for discovering valuable microbial metabolites using innovative strategies like OSMAC and machine learning to boost drug development.

## Contribution

The paper introduces a comprehensive framework integrating OSMAC and genomics with machine learning for efficient microbial natural product discovery.

## Key findings

- OSMAC and genomics-driven approaches are overcoming cultivation limitations in microbial metabolite discovery.
- Machine learning is enabling faster identification of bioactive compounds with novel structures and mechanisms.
- Case studies from 2019 to 2025 highlight newly discovered compounds with potential for antibiotics and therapeutics.

## Abstract

Microorganisms represent Earth's most abundant biological resource, producing metabolites of immense value across medicine, agriculture, and industry. Conventional cultivation and screening techniques, however, suffer from inefficiency and fail to meet contemporary demands. Providing a comprehensive overview, this review details how the One Strain Many Compounds (OSMAC) strategy—addressing cultivation bottlenecks—and genomics-driven mining approaches are revolutionizing the discovery of novel microbial metabolites. Crucially, it underscores the broad adoption of innovative technologies like machine learning to enable faster, more effective gene and structure targeting. Synthesizing case studies from 2019 to 2025, the review catalogs newly identified compounds and their bioactivities, while outlining future research directions to establish a theoretical framework for efficient microbial natural product exploration. These advanced discovery strategies are significantly accelerating the identification of structurally diverse lead compounds with novel mechanisms of action, thereby revitalizing pipelines for new antibiotic, anticancer, and therapeutic drug development.

The online version contains supplementary material available at 10.1007/s13659-025-00565-0.

## Full-text entities

- **Genes:** IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, SI (sucrase-isomaltase) [NCBI Gene 6476], HSD17B6 (hydroxysteroid 17-beta dehydrogenase 6) [NCBI Gene 8630] {aka HSE, RODH, SDR9C6}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, ACHE (acetylcholinesterase (Yt blood group)) [NCBI Gene 43] {aka ACEE, ARACHE, N-ACHE, YT}, CAVIN2 (caveolae associated protein 2) [NCBI Gene 8436] {aka PS-p68, SDPR, SDR, cavin-2}, AURKB (aurora kinase B) [NCBI Gene 9212] {aka AIK2, AIM-1, AIM1, ARK-2, ARK2, AurB}, caspa (caspase a) [NCBI Gene 57933] {aka casp1, caspy, fa93b02, wu:fa93b02, zgc:109869}, TAM (Myeloproliferative syndrome, transient (transient abnormal) [NCBI Gene 8205] {aka MST}, CYP2B6 (cytochrome P450 family 2 subfamily B member 6) [NCBI Gene 1555] {aka CPB6, CYP2B, CYP2B7, CYPIIB6, EFVM, IIB1}, KARS1 (lysyl-tRNA synthetase 1) [NCBI Gene 3735] {aka CMTRIB, DEAPLE, DFNB89, KARS, KARS2, KRS}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, ALKBH1 (alkB homolog 1, histone H2A dioxygenase) [NCBI Gene 8846] {aka ABH, ABH1, ALKBH, alkB, hABH}
- **Diseases:** cancer (MESH:D009369), leukemia (MESH:D007938), melanoma (MESH:D008545), anti (MESH:D006679), liver fibrosis (MESH:D008103), cytotoxic (MESH:D064420), infective (MESH:D007239), Clostridioides difficile (MESH:D003015), pancreatic cancer (MESH:D010190), liver injury (MESH:D017093), neuroblastoma (MESH:D009447), breast, ovarian, and melanoma cancer (MESH:D061325), Fungal (MESH:D009181), inflammatory (MESH:D007249), Parkinson's disease (MESH:D010300), breast cancer (MESH:D001943), Acinetobacter baumannii infections (MESH:D000151)
- **Chemicals:** squalene (MESH:D013185), 1-benzazepine- (-), sphingolipids (MESH:D013107), platensimycin (MESH:C510909), sodium butyrate (MESH:D020148), 3,5-dimethylorsellinic acid (MESH:C000624496), DMTD (MESH:C033016), paclitaxel (MESH:D017239), sesquiterpene (MESH:D012717), oxalic acid (MESH:D019815), KI (MESH:C066186), triterpenoids (MESH:D014315), iron (MESH:D007501), peptides (MESH:D010455), cichorine (MESH:C504968), vancomycin (MESH:D014640), B (MESH:D001895), lovastatin (MESH:D008148), dioxolane (MESH:C010962), 5-Aza (MESH:D001374), Phenalenones (MESH:C038036), polyketide (MESH:D061065), polyamine (MESH:D011073), NO (MESH:D009614), cyclopentenones (MESH:C013905), ether (MESH:D004986), N ( (MESH:D009584), DM27 (MESH:C495413), L (MESH:D007930), xanthone (MESH:C009689), CoCl2 (MESH:C018021), sclerotiorin (MESH:C101449), carbapenem (MESH:D015780), halicin (MESH:C000717882), tryptophan (MESH:D014364), cyclopentane (MESH:D003517), SAHA (MESH:D000077337), kojic acid (MESH:C011890), diterpene (MESH:D004224), cytochalasins (MESH:D003572), amino acid (MESH:D000596), salt (MESH:D012492), agarose (MESH:D012685), enterobactin (MESH:D004758), OCA (MESH:C464660), Kyn (MESH:D007737), rapamycin (MESH:D020123), I (MESH:D007455), acetaminophen (MESH:D000082), F (MESH:D005461), octadecadienoic acid (MESH:C027369), NaNO3 (MESH:C031618), J (MESH:C000608249), cholesterol (MESH:D002784), azaphilone (MESH:C494154), amphotericin B. (MESH:D000666), butyrolactone (MESH:D015107), herquline A (MESH:C022235), polysaccharides (MESH:D011134), H (MESH:D006859)
- **Species:** Trametes versicolor (turkey-tail fungus, species) [taxon 5325], Influenza A virus (no rank) [taxon 11320], Penicillium bialowiezense (species) [taxon 293381], Penicillium canescens (species) [taxon 5083], Edwardsiella tarda (species) [taxon 636], Alternaria alternata (species) [taxon 5599], Fusarium sp. (species) [taxon 29916], Houttuynia cordata (chameleon-plant, species) [taxon 16752], Amphichorda sp. (species) [taxon 2011980], Stachybotrys chartarum (species) [taxon 74722], Staphylococcus aureus (species) [taxon 1280], Micrococcus luteus (species) [taxon 1270], Ganoderma gibbosum (species) [taxon 34460], Armillaria sp. (species) [taxon 1906949], Aspergillus terreus (species) [taxon 33178], Xanthomonas oryzae (species) [taxon 347], Phoenix dactylifera (date palm, species) [taxon 42345], Penicillium ochrochloron (species) [taxon 69780], Eutypella sp. (species) [taxon 1715228], Zymoseptoria tritici (species) [taxon 1047171], Talaromyces sp. (species) [taxon 1707706], Monascus purpureus (species) [taxon 5098], Enterobacteriaceae (enterobacteria, family) [taxon 543], Phoma sp. (species) [taxon 1707701], Aspergillus calidoustus (species) [taxon 454130], Cercospora zeae-maydis (species) [taxon 135779], Penicillium camemberti (species) [taxon 5075], Calcarisporium arbuscula (species) [taxon 240499], Phomopsis sp. (species) [taxon 1715245], Irpex lacteus (species) [taxon 5319], Penicillium sp. (species) [taxon 5081], Epicoccum dendrobii (species) [taxon 2021033], Nigrospora oryzae (species) [taxon 335854], Cryptococcus neoformans (Cryptococcus neoformans serotype A, species) [taxon 5207], Gadidae sp. A02 (species) [taxon 2727005], Danio rerio (leopard danio, species) [taxon 7955], Human immunodeficiency virus 1 (no rank) [taxon 11676], Bacillus subtilis (species) [taxon 1423], Tsukamurella pulmonis (species) [taxon 47312], Oryza sativa (Asian cultivated rice, species) [taxon 4530], Chaetomium globosporum [taxon 941763], Herpotrichia sp. (species) [taxon 1755428], Trichocladium sp. (species) [taxon 1756122], Penicillium bilaiae (species) [taxon 69765], Phellinus orientoasiaticus (species) [taxon 1825552], Penicillium chermesinum (species) [taxon 63820], Mycobacterium tuberculosis (species) [taxon 1773], Trichoderma (genus) [taxon 5543], Pantoea agglomerans (species) [taxon 549], Candida albicans (species) [taxon 5476], Homo sapiens (human, species) [taxon 9606], Pyricularia oryzae (rice blast fungus, species) [taxon 318829], Daldinia eschscholtzii (species) [taxon 292717], Penicillium janthinellum (species) [taxon 5079], Pleotrichocladium opacum (species) [taxon 2016671], Vanderbylia robiniophila (species) [taxon 526246], Pestalotiopsis sp. (species) [taxon 36460], Fungi (kingdom) [taxon 4751], Leohumicola minima (species) [taxon 290618], Halobacillus sp. K16 (species) [taxon 1792195]
- **Cell lines:** HL-60 — Homo sapiens (Human), Adult acute myeloid leukemia with maturation, Cancer cell line (CVCL_0002), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), SW480 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0546), UR59 — Homo sapiens (Human), Renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions, Cancer cell line (CVCL_6997), PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481), MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), HEL — Homo sapiens (Human), Erythroleukemia, Cancer cell line (CVCL_0001), HOK021 — Hexagrammos otakii (Fat greenling), Spontaneously immortalized cell line (CVCL_YE19), MDA-MB-435 — Homo sapiens (Human), Amelanotic melanoma, Cancer cell line (CVCL_0417), RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), 293FT — Homo sapiens (Human), Transformed cell line (CVCL_6911), SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019), LX-2 — Homo sapiens (Human), Transformed cell line (CVCL_5792), L1210 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0382), H1299 — Homo sapiens (Human), Lung large cell carcinoma, Cancer cell line (CVCL_0060), H9c2 — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_0286), H1975 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_1511)

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12790562