Induction of Fungal Secondary Metabolites by Co-Culture with Actinomycete Producing HDAC Inhibitor Trichostatins
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A recently bioinformatic analysis of genomic sequences of fungi indicated that fungi are able to produce more secondary metabolites than expected. Despite their potency, many biosynthetic pathways are silent in the absence of specific culture conditions or chemical cues. To access cryptic metabolism, 108 fungal strains isolated from various sites were cultured with or without Streptomyces sp. 13F051 which mainly produces trichostatin analogues, followed by comparison of metabolic profiles using LC-MS. Among the 108 fungal strains, 14 produced secondary metabolites that were not recognized or were scarcely produced in mono-cultivation. Of these two fungal strains, Myrmecridium schulzeri 15F098 and Scleroconidioma sphagnicola 15S058 produced four new compounds (1-4) along with a known compound (5), demonstrating that all four compounds were produced by physical interaction with Streptomyces sp. 13F051. Bioactivity evaluation indicated that compounds 3-5 impede migration of MDA-MB-231 breast cancer cells.
Abstract
A recently bioinformatic analysis of genomic sequences of fungi indicated that fungi are able to produce more secondary metabolites than expected. Despite their potency, many biosynthetic pathways are silent in the absence of specific culture conditions or chemical cues. To access cryptic metabolism, 108 fungal strains isolated from various sites were cultured with or without Streptomyces sp. 13F051 which mainly produces trichostatin analogues, followed by comparison of metabolic profiles using LC-MS. Among the 108 fungal strains, 14 produced secondary metabolites that were not recognized or were scarcely produced in mono-cultivation. Of these two fungal strains, Myrmecridium schulzeri 15F098 and Scleroconidioma sphagnicola 15S058 produced four new compounds (1-4) along with a known compound (5), demonstrating that all four compounds were produced by physical interaction with Streptomyces sp. 13F051. Bioactivity evaluation indicated that compounds 3-5 impede migration of MDA-MB-231 breast cancer cells.
참고문헌 (26)
- Schueffler A, "Fungal natural products in research and development", Nat. Prod. Rep, 31, pp.1425~1448 (2014)
- Blackwell M, "The fungi: 1, 2, 3 ... 5.1 million species?", Am. J. Bot, 98, pp.426~438 (2011)
- Robey MT, "An interpreted atlas of biosynthetic gene clusters from 1,000 fungal genomes", Proc. Natl. Acad. Sci. USA, 118(19), pp.e2020230118~ (2021)
- Monciardini P, "Discovering new bioactive molecules from microbial sources", Microb. Biotechnol, 7, pp.209~220 (2014)
- Hautbergue T, "From genomics to metabolomics, moving toward an integrated strategy for the discovery of fungal secondary metabolites", Nat. Prod. Rep, 35, pp.147~173 (2018)
- Scherlach K, "Triggering cryptic natural product biosynthesis in microorganisms", Org. Biomol. Chem, 7, pp.1753~1760 (2009)
- Netzker T, "Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters", Front. Microbiol, 6, pp.299~ (2015)
- Keller NP, "Fungal secondary metabolism: regulation, function and drug discovery", Nat. Rev. Microbiol, 17, pp.167~180 (2019)
- Bertrand S, "Metabolite induction via microorganism co-culture: a potential way to enhance chemical diversity for drug discovery", Biotechnol. Adv, 32, pp.1180~1204 (2014)
- Arora D, "Expanding the chemical diversity through microorganisms coculture:Current status and outlook", Biotechnol. Adv, 40, pp.107521~ (2020)
- Williams RB, "Epigenetic remodeling of the fungal secondary metabolome", Org. Biomol. Chem, 6, pp.1895~1897 (2008)
- Cherblanc FL, "Perspectives on natural product epigenetic modulators in chemical biology and medicine", Nat. Prod. Rep, 30, pp.605~624 (2013)
- Son S, "Ulleungamides A and B, modified alpha,beta-dehydropipecolic acid containing cyclic depsipeptides from Streptomyces sp. KCB13F003", Org. Lett, 17, pp.4046~4049 (2015)
- Finnin MS, "Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors", Nature, 401, pp.188~193 (1999)
- Zutz C, "Small chemical chromatin effectors alter secondary metabolite production in Aspergillus clavatus", Toxins (Basel), 5, pp.1723~1741 (2013)
- Ohsumi K, "AS2077715: a novel antifungal antibiotic produced by Capnodium sp. 339855", J. Antibiot. (Tokyo), 67, pp.707~711 (2014)
- Yu NH, "Endophytic and endolichenic fungal diversity in maritime Antarctica based on cultured material and their evolutionary position among Dikarya", Fungal Syst. Evol, 2, pp.263~272 (2018)
- Kawamoto K, "Production of monapinones by fermentation of the dinapinone-producing fungus Penicillium pinophilum FKI-3864 in a seawater-containing medium", J. Antibiot. (Tokyo), 64, pp.503~508 (2011)
- Ohte S, "Dinapinones, novel inhibitors of triacylglycerol synthesis in mammalian cells, produced by Penicillium pinophilum FKI-3864", J. Antibiot. (Tokyo), 64, pp.489~494 (2011)
- Uchida R, "Structures and absolute stereochemistry of dinapinones A1 and A2, inhibitors of triacylglycerol synthesis, produced by penicillium pinophilum FKI-3864", J. Antibiot. (Tokyo), 65, pp.419~425 (2012)
- Kawaguchi M, "New dinapinone derivatives, potent inhibitors of triacylglycerol synthesis in mammalian cells, produced by Talaromyces pinophilus FKI-3864", J. Antibiot. (Tokyo), 66, pp.179~189 (2013)
- Kim J, "Sambutoxin-producing isolates of fusarium species and occurrence of sambutoxin in rotten potato tubers", Appl. Environ. Microbiol, 61, pp.3750~3751 (1995)
- Jayasinghe L, "N-Methyl-4-hydroxy-2-pyridinone analogues from Fusarium oxysporum", J. Nat. Prod, 69, pp.439~442 (2006)
- Schmidt Y, "Direct assignment of the relative configuration in 1,3,n-methyl-branched carbon chains by 1H NMR spectroscopy", Org. Lett, 12, pp.2218~2221 (2010)
- Gupta GP, "Cancer metastasis: building a framework", Cell, 127, pp.679~695 (2006)
- Hoshino S, "Activation of silent biosynthetic pathways and discovery of novel secondary metabolites in actinomycetes by co-culture with mycolic acid-containing bacteria", J. Ind. Microbiol. Biotechnol, 46, pp.363~374 (2019)