Abstract
Fungal secondary metabolites (SMs) with therapeutic potential have played and continue to play an important role in new drug discovery. These substances are biosynthetically formed through a series of sequential reactions catalyzed by SM biosynthetic gene cluster (BGC)-encoded enzymes. However, most of these BGCs are silent or expressed in low level under conventional cultivation and fermentation conditions. It frequently results in the rediscovery of the same metabolites from various strains, and the speed of discovery of novel fungal SM is slowing down. In order to alleviate this challenge, one strain many compounds (OSMAC) strategy has become the most effective and simple approach to awaken these cryptic BGCs. A great number of successful examples using this strategy to enhance chemical diversity of fungal SM are comprehensively summarized in this chapter.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adpressa DA, Loesgen S (2016) Bioprospecting chemical diversity and bioactivity in a marine derived Aspergillus terreus. Chem Biodivers 13(2):253–259
Ancheeva E, Kueppers L, Akone SH, Ebrahim W, Liu Z, Mandi A, Kurtan T, Lin W, Orfali R, Rehberg N, Kalscheuer R, Daletos G, Proksch P (2017) Expanding the metabolic profile of the fungus Chaetomium sp through co-culture with autoclaved Pseudomonas aeruginosa. Eur J Org Chem 2017(22):3256–3264
Araujo FD, Croteau S, Slack AD, Milutinovic S, Bigey P, Price GB, Zannis-Hajopoulos M, Szyf M (2001) The DNMT1 target recognition domain resides in the N terminus. J Biol Chem 276(10):6930–6936
Ariantari NP, Daletos G, Mandi A, Kurtan T, Muller WEG, Lin W, Ancheeva E, Proksch P (2019) Expanding the chemical diversity of an endophytic fungus Bulgaria inquinans, an ascomycete associated with mistletoe, through an OSMAC approach. RSC Adv 9(43):25119–25132
Asai T, Yamamoto T, Oshima Y (2011) Histone deacetylase inhibitor induced the production of three novel prenylated tryptophan analogs in the entomopathogenic fungus, Torrubiella luteorostrata. Tetrahedron Lett 52(52):7042–7045
Asai T, Chung YM, Sakurai H, Ozeki T, Chang FR, Wu YC, Yamashita K, Oshima Y (2012a) Highly oxidized ergosterols and isariotin analogs from an entomopathogenic fungus, Gibellula formosana, cultivated in the presence of epigenetic modifying agents. Tetrahedron 68(29):5817–5823
Asai T, Chung YM, Sakurai H, Ozeki T, Chang FR, Yamashita K, Oshima Y (2012b) Tenuipyrone, a novel skeletal polyketide from the entomopathogenic fungus, Isaria tenuipes, cultivated in the presence of epigenetic modifiers. Org Lett 14(2):513–515
Asai T, Luo D, Obara Y, Taniguchi T, Monde K, Yamashita K, Oshima Y (2012c) Dihydrobenzofurans as cannabinoid receptor ligands from Cordyceps annullata, an entomopathogenic fungus cultivated in the presence of an HDAC inhibitor. Tetrahedron Lett 53(17):2239–2243
Asai T, Morita S, Shirata N, Taniguchi T, Monde K, Sakurai H, Ozeki T, Oshima Y (2012d) Structural diversity of new C-13-polyketides produced by Chaetomium mollipilium cultivated in the presence of a NAD(+)-dependent histone deacetylase inhibitor. Org Lett 14(21):5456–5459
Asai T, Yamamoto T, Chung YM, Chang FR, Wu YC, Yamashita K, Oshima Y (2012e) Aromatic polyketide glycosides from an entomopathogenic fungus, Cordyceps indigotica. Tetrahedron Lett 53(3):277–280
Asai T, Yamamoto T, Oshima Y (2012f) Aromatic polyketide production in Cordyceps indigotica, an entomopathogenic fungus, induced by exposure to a histone deacetylase inhibitor. Org Lett 14(8):2006–2009
Asai T, Otsuki S, Sakurai H, Yamashita K, Ozeki T, Oshima Y (2013a) Benzophenones from an endophytic fungus, Graphiopsis chlorocephala, from Paeonia lactiflora cultivated in the presence of an NAD(+)-dependent HDAC inhibitor. Org Lett 15(8):2058–2061
Asai T, Taniguchi T, Yamamoto T, Monde K, Oshima Y (2013b) Structures of spiroindicumides a and B, unprecedented carbon skeletal spirolactones, and determination of the absolute configuration by vibrational circular dichroism exciton approach. Org Lett 15(17):4320–4323
Asai T, Yamamoto T, Shirata N, Taniguchi T, Monde K, Fujii I, Gomi K, Oshima Y (2013c) Structurally diverse chaetophenol productions induced by chemically mediated epigenetic manipulation of fungal gene expression. Org Lett 15(13):3346–3349
Asai T, Morita S, Taniguchi T, Monde K, Oshima Y (2016) Epigenetic stimulation of polyketide production in Chaetomium cancroideum by an NAD(+)-dependent HDAC inhibitor. Org Biomol Chem 14(2):646–651
Barros-Filho BA, Oliveira MCF, Mafezoli J, Barbosa FG, Rodrigues-Filho E (2012) Secondary metabolite production by the basidiomycete, Lentinus strigellus, under different culture conditions. Nat Prod Commun 7(6):771–773
Basiacik Karakoc S, Aksoz N (2004) Optimization of carbon-nitrogen ratio for production of gibberellic acid by pseudomonas sp. Pol J Microbiol 53(2):117–120
Blunt JW, Copp BR, Keyzers RA, Munro MHG, Prinsep MR (2017) Marine natural products. Nat Prod Rep 34(3):235–294
Bode HB, Zeeck A (2000) Sphaerolone and dihydrosphaerolone, two bisnaphthyl-pigments from the fungus Sphaeropsidales sp F-24’ 707. Phytochemistry 54(6):597–601
Bode HB, Bethe B, Hofs R, Zeeck A (2002) Big effects from small changes: pdxossible ways to explore nature’s chemical diversity. Chembiochem 3(7):619–627
Bohni N, Cordero-Maldonado ML, Maes J, Siverio-Mota D, Marcourt L, Munck S, Kamuhabwa AR, Moshi MJ, Esguerra CV, Witte PAM, Crawford AD, Wolfender JL (2013) Integration of microfractionation, qNMR and zebrafish screening for the in vivo bioassay-guided isolation and quantitative bioactivity analysis of natural roducts. PLoS One 8(5):e64006
Brzonkalik K, Huemmer D, Syldatk C, Neumann A (2012) Influence of pH and carbon to nitrogen ratio on mycotoxin production by Alternaria alternata in submerged cultivation. AMB Express 2:28
Chen HJ, Awakawa T, Sun JY, Wakimoto T, Abe I (2013) Epigenetic modifier-induced biosynthesis of novel fusaric acid derivatives in endophytic fungi from Datura stramonium L. Nat Prod Bioprospect 3(1):20–23
Chen H, Daletos G, Abdel-Aziz MS, Thomy D, Dai H, Broetz-Oesterhelt H, Lin W, Proksch P (2015) Inducing secondary metabolite production by the soil-dwelling fungus Aspergillus terreus through bacterial co-culture. Phytochem Lett 12:35–41
Chen M, Zhang W, Shao CL, Chi ZM, Wang CY (2016) DNA methyltransferase inhibitor induced fungal biosynthetic products: diethylene glycol phthalate ester oligomers from the marine-derived fungus Cochliobolus lunatus. Mar Biotechnol 18(3):409–417
Chen Y, Yang W, Zou G, Wang G, Kang W, Yuan J, She Z (2022) Cytotoxic bromine- and iodine-containing cytochalasins produced by the mangrove endophytic fungus Phomopsis sp. QYM-13 using the OSMAC approach. J Nat Prod 85(5):1229–1238
Christian OE, Compton J, Christian KR, Mooberry SL, Valeriote FA, Crews P (2005) Using jasplakinolide to turn on pathways that enable the isolation of new chaetoglobosins from Phomospis asparagi. J Nat Prod 68(11):1592–1597
Chung YM, El-Shazly M, Chuang DW, Hwang TL, Asai T, Oshima Y, Ashour ML, Wu YC, Chang FR (2013a) Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, induces the production of anti-inflammatory cyclodepsipeptides from Beauveria felina. J Nat Prod 76(7):1260–1266
Chung YM, Wei CK, Chuang DW, El-Shazly M, Hsieh CT, Asai T, Oshima Y, Hsieh TJ, Hwang TL, Wu YC, Chang FR (2013b) An epigenetic modifier enhances the production of anti-diabetic and anti-inflammatory sesquiterpenoids from Aspergillus sydowii. Bioorg Med Chem 21(13):3866–3872
Cole PA (2008) Chemical probes for histone-modifying enzymes. Nat Chem Biol 4(10):590–597
Degenkolb T, Heinze S, Schlegel B, Strobel G, Grafe U (2002) Formation of new lipoaminopeptides, acremostatins a, B, and C, by co-cultivation of Acremonium sp Tbp-5 and Mycogone rosea DSM 12973. Biosci Biotechnol Biochem 66(4):883–886
Deng ZL, Du CX, Li X, Hu B, Kuang ZK, Wang R, Peng SY, Zhang HY, Kong DX (2013) Exploring the biologically relevant chemical space for drug discovery. J Chem Inf Model 53(11):2820–2828
Dinarvand M, Rezaee M, Masomian M, Jazayeri SD, Zareian M, Abbasi S, Ariff AB (2013) Effect of C/N ratio and media optimization through response surface methodology on simultaneous productions of intra- and extracellular inulinase and invertase from Aspergillus Niger ATCC 20611. Biomed Res Int 2013:508968
Ding G, Liu S, Guo L, Zhou Y, Che Y (2008) Antifungal metabolites from the plant endophytic fungus Pestalotiopsis foedan. J Nat Prod 71(4):615–618
Ding G, Zheng Z, Liu S, Zhang H, Guo L, Che Y (2009) Photinides A-F, cytotoxic benzofuranone-derived gamma-lactones from the plant endophytic fungus Pestalotiopsis photiniae. J Nat Prod 72(5):942–945
Ding G, Qi Y, Liu S, Guo L, Chen X (2012) Photipyrones a and B, new pyrone derivatives from the plant endophytic fungus Pestalotiopsis photiniae. J Antibiot 65(5):271–273
Dong YS, Yang JS, Zhang H, Lin J, Ren X, Liu M, Lu XH, He JG (2006) Wortmannilactones A-D, 22-membered triene macrolides from Talaromyces wortmannii. J Nat Prod 69(1):128–130
Dong Y, Lin J, Lu X, Zheng Z, Ren X, Zhang H, He J, Yang J (2009) Cathepsin B inhibitory tetraene lactones from the fungus Talaromyces wortmannii. Helv Chim Acta 92(3):567–574
Du L, Li D, Zhu T, Cai S, Wang F, Xiao X, Gu Q (2009) New alkaloids and diterpenes from a deep ocean sediment derived fungus Penicillium sp. Tetrahedron 65(5):1033–1039
Du L, Feng T, Zhao B, Li D, Cai S, Zhu T, Wang F, Xiao X, Gu Q (2010) Alkaloids from a deep ocean sediment-derived fungus Penicillium sp and their antitumor activities. J Antibiot 63(4):165–170
Du L, King JB, Cichewicz RH (2014) Chlorinated polyketide obtained from a Daldinia sp treated with the epigenetic modifier suberoylanilide hydroxamic acid. J Nat Prod 77(11):2454–2458
Ebrahim W, El-Neketi M, Lewald LI, Orfali RS, Lin W, Rehberg N, Kalscheuer R, Daletos G, Proksch P (2016) Metabolites from the fungal endophyte Aspergillus austroafricanus in axenic culture and in fungal-bacterial mixed cultures. J Nat Prod 79(4):914–922
El-Kashef DH, Youssef FS, Hartmann R, Knedel TO, Janiak C, Lin W, Reimche I, Teusch N, Liu Z, Proksch P (2020) Azaphilones from the red sea fungus Aspergillus falconensis. Mar Drugs 18(4):204
Elnaggar MS, Ebada SS, Ashour ML, Ebrahim W, Mueller WEG, Mandi A, Kurtan T, Singab A, Lin W, Liu Z, Proksch P (2016) Xanthones and sesquiterpene derivatives from a marine-derived fungus Scopulariopsis sp. Tetrahedron 72(19):2411–2419
Elnaggar MS, Ebada SS, Ashour ML, Ebrahim W, Singab A, Lin W, Liu Z, Proksch P (2017) Two new triterpenoids and a new naphthoquinone derivative isolated from a hard coral-derived fungus Scopulariopsis sp. Fitoterapia 116:126–130
Elsard SS, Trusch F, Deng H, Raab A, Prokes I, Busarakam K, Asenjo JA, Andrews BA, West P, Bull AT, Goodfellow M, Yi Y, Ebel R, Jaspars M, Rateb ME (2015) Chaxapeptin, a lasso peptide from extremotolerant Streptomyces leeuwenhoekii strain C58 from the hyperarid Atacama desert. J Org Chem 80(20):10252–10260
Feller G, Narinx E, Arpigny JL, Zekhnini Z, Swings J, Gerday C (1994) Temperature-dependence of growth, enzyme- secretion and activty of psychrophilic antarctic bacteria. Appl Microbiol Biotechnol 41(4):477–479
Frank M, Ozkaya FC, Mueller WEG, Hamacher A, Kassack MU, Lin W, Liu Z, Proksch P (2019) Cryptic secondary metabolites from the sponge-associated fungus Aspergillus ochraceus. Mar Drugs 17(2):99
Fuchser J, Thiericke R, Zeeck A (1995) Biosynthesis of aspinonene, a branched pentaketide produced by Aspergllus ochraceus, related to aspyrone. J Chem Soc Perkin Trans 1(13):1663–1666
Fukuda H, Sano N, Muto S, Horikoshi M (2006) Simple histone acetylation plays a complex role in the regulation of gene expression. Brief Funct Genomic Proteomic 5(3):190–208
Gao SS, Li XM, Zhang Y, Li CS, Cui CM, Wang BG (2011) Comazaphilones A-F, azaphilone derivatives from the marine sediment-derived fungus Penicillium commune QSD-17. J Nat Prod 74(2):256–261
Gao SS, Shang Z, Li XM, Li CS, Cui CM, Wang BG (2012) Secondary metabolites produced by solid fermentation of the marine-derived fungus Penicillium commune QSD-17. Biosci Biotechnol Biochem 76(2):358–360
Gao H, Zhou L, Cai S, Zhang G, Zhu T, Gu Q, Li D (2013) Diorcinols B-E, new prenylated diphenyl ethers from the marine-derived fungus Aspergillus versicolor ZLN-60. J Antibiot 66(9):539–542
Gao Y, Stuhldreier F, Schmitt L, Wesselborg S, Guo Z, Zou K, Mandi A, Kurtan T, Liu Z, Proksch P (2020) Induction of new lactam derivatives from the endophytic fungus Aplosporella javeedii through an OSMAC approach. Front Microbiol 11:600983
Gibson AM, Bratchell N, Roberts TA (1988) Predicting microbial growth: growth responses of salmonellae in a laboratory medium as affected by pH, sodium chloride and storage temperature. Int J Food Microbiol 6(2):155–178
Gulder TAM, Hong H, Correa J, Egereva E, Wiese J, Imhoff JF, Gross H (2012) Isolation, structure elucidation and total synthesis of lajollamide a from the marine fungus Asteromyces cruciatus. Mar Drugs 10(12):2912–2935
Gunatilaka AAL (2006) Natural products from plant-associated microorganisms: distribution, structural diversity, bioactivity, and implications of their occurrence. J Nat Prod 69(3):509–526
Guo W, Peng J, Zhu T, Gu Q, Keyzers RA, Li D (2013) Sorbicillamines A-E, nitrogen-containing sorbicillinoids from the deep-sea-derived fungus Penicillium sp F23-2. J Nat Prod 76(11):2106–2112
Hemphill CFP, Sureechatchaiyan P, Kassack MU, Orfali RS, Lin W, Daletos G, Proksch P (2017) OSMAC approach leads to new fusarielin metabolites from Fusarium tricinctum. J Antibiot 70(6):726–732
Henrikson JC, Hoover AR, Joyner PM, Cichewicz RH (2009) A chemical epigenetics approach for engineering the in situ biosynthesis of a cryptic natural product from Aspergillus Niger. Org Biomol Chem 7(3):435–438
Hewage RT, Aree T, Mahidol C, Ruchirawat S, Kittakoop P (2014) One strain-many compounds (OSMAC) method for production of polyketides, azaphilones, and an isochromanone using the endophytic fungus Dothideomycete sp. Phytochemistry 108:87–94
Hug JJ, Bader CD, Remskar M, Cirnski K, Mueller R (2018) Concepts and methods to access novel antibiotics from actinomycetes. Antibiotics 7(2):44
Jiang W, Zhong Y, Shen L, Wu X, Ye Y, Chen CTA, Wu B (2014) Stress-driven discovery of natural products from extreme marine environment-kueishantao hydrothermal vent, a case study of metal switch valve. Curr Org Chem 18(7):925–934
Kakeya H, Morishita M, Onozawa C, Usami R, Horikoshi K, Kimura K, Yoshihama M, Osada H (1997) RKS-1778, a new mammalian cell-cycle inhibitor and a key intermediate of the 11 cytochalasin group. J Nat Prod 60(7):669–672
Kamauchi H, Kinoshita K, Sugita T, Koyama K (2016) Conditional changes enhanced production of bioactive metabolites of marine derived fungus Eurotium rubrum. Bioorg Med Chem Lett 26(20):4911–4914
Keller NP (2019) Fungal secondary metabolism: regulation, function and drug discovery. Nat Rev Microbiol 17(3):167–180
Kueck U, Bloemendal S, Teichert I (2014) Putting fungi to work: harvesting a cornucopia of drugs, toxins, and antibiotics. PLoS Pathog 10(3):e1003950
Lei H, Bi X, Lin X, She J, Luo X, Niu H, Zhang D, Yang B (2021) Heterocornols from the sponge-derived fungus pestalotiopsis heterocornis with anti-inflammatory activity. Mar Drugs 19(11):585
Li CS, An CY, Li XM, Gao SS, Cui CM, Sun HF, Wang BG (2011) Triazole and dihydroimidazole alkaloids from the marine sediment-derived fungus Penicillium paneum SD-44. J Nat Prod 74(5):1331–1334
Li CS, Li XM, Gao SS, Lu YH, Wang BG (2013) Cytotoxic anthranilic acid derivatives from deep sea sediment-derived fungus Penicillium paneum SD-44. Mar Drugs 11(8):3068–3076
Li G, Kusari S, Golz C, Laatsch H, Strohmann C, Spiteller M (2017a) Epigenetic modulation of endophytic Eupenicillium sp LG41 by a histone deacetylase inhibitor for production of decalin-containing compounds. J Nat Prod 80(4):983–988
Li X, Xia Z, Tang J, Wu J, Tong J, Li M, Ju J, Chen H, Wang L (2017b) Identification and biological evaluation of secondary metabolites from marine derived fungi Aspergillus sp. SCSIOW3, cultivated in the presence of epigenetic modifying agents. Molecules 22(8):1302
Li Y, Wang J, He W, Lin X, Zhou X, Liu Y (2017c) One strain-many compounds method for production of polyketide metabolites using the sponge-derived fungus Arthrinium arundinis ZSDS1-F3. Chem Nat Compd 53(2):373–374
Li W, Ding L, Wang N, Xu J, Zhang W, Zhang B, He S, Wu B, Jin H (2019) Isolation and characterization of two new metabolites from the sponge-derived fungus Aspergillus sp. LS34 by OSMAC approach. Mar Drugs 17(5):283
Lin ZJ, Zhu TJ, Zhang GJ, Wei HJ, Gu QQ (2009a) Deoxy-cytochalasins from a marine-derived fungus Spicaria elegans. Can J Chem 87(3):486–489
Lin Z, Zhu T, Wei H, Zhang G, Wang H, Gu Q (2009b) Spicochalasin a and new aspochalasins from the marine-derived fungus Spicaria elegans. Eur J Org Chem 2009(18):3045–3051
Lin ZJ, Zhu TJ, Chen L, Gu QQ (2010) Three new aspochalasin derivatives from the marine-derived fungus Spicaria elegans. Chin Chem Lett 21(7):824–826
Liu R, Gu QQ, Zhu WM, Cui CB, Fan GT (2005) Trichodermamide a and aspergillazine a, two cytotoxic modified dipeptides from a marine-derived fungus Spicaria elegans. Arch Pharm Res 28(9):1042–1046
Liu R, Gu Q, Zhu W, Cui C, Fan G, Fang Y, Zhu T, Liu H (2006) 10-phenyl- 12 -cytochalasins Z(7), Z(8), and Z(9) from the marine-derived fungus Spicaria elegans. J Nat Prod 69(6):871–875
Liu L, Liu S, Jiang L, Chen X, Guo L, Che Y (2008a) Chloropupukeananin, the first chlorinated pupukeanane derivative, and its precursors from Pestalotiopsis fici. Org Lett 10(7):1397–1400
Liu L, Tian R, Liu S, Chen X, Guo L, Che Y (2008b) Pestaloficiols A-E, bioactive cyclopropane derivatives from the plant endophytic fungus Pestalotiopsis fici. Bioorg Med Chem 16(11):6021–6026
Liu R, Lin Z, Zhu T, Fang Y, Gu Q, Zhu W (2008c) Novel open-chain cytochalasins from the marine-derived fungus Spicaria elegans. J Nat Prod 71(7):1127–1132
Liu L, Li Y, Liu S, Zheng Z, Chen X, Zhang H, Guo L, Che Y (2009a) Chloropestolide a, an antitumor metabolite with an unprecedented spiroketal skeleton from Pestalotiopsis fici. Org Lett 11(13):2836–2839
Liu L, Liu S, Niu S, Guo L, Chen X, Che Y (2009b) Isoprenylated chromone derivatives from the plant endophytic fungus Pestalotiopsis fici. J Nat Prod 72(8):1482–1486
Liu L, Niu S, Lu X, Chen X, Zhang H, Guo L, Che Y (2010) Unique metabolites of Pestalotiopsis fici suggest a biosynthetic hypothesis involving a Diels-Alder reaction and then mechanistic diversification. Chem Commun 46(3):460–462
Liu L, Bruhn T, Guo L, Goetz DCG, Brun R, Stich A, Che Y, Bringmann G (2011) Chloropupukeanolides C-E: cytotoxic pupukeanane chlorides with a spiroketal skeleton from Pestalotiopsis fici. Chem Eur J 17(9):2604–2613
Liu Y, Li XM, Meng LH, Jiang WL, Xu GM, Huang CG, Wang BG (2015) Bisthiodiketopiperazines and acorane sesquiterpenes produced by the marine-derived fungus Penicillium adametzioides AS-53 on different culture media. J Nat Prod 78(6):1294–1299
Liu WC, Yang F, Zhang R, Shi X, Lu XH, Luan YS, Xiu ZL, Dong YS (2016) Production of polyketides with anthelmintic activity by the fungus Talaromyces wortmannii using one strain-many compounds (OSMAC) method. Phytochem Lett 18:157–161
Liu S, Dai H, Heering C, Janiak C, Lin W, Liu Z, Proksch P (2017) Inducing new secondary metabolites through co-cultivation of the fungus Pestalotiopsis sp with the bacterium Bacillus subtilis. Tetrahedron Lett 58(3):257–261
Liu DS, Rong XG, Kang HH, Ma LY, Hamann MT, Liu WZ (2018) Raistrickiones A-E from a highly productive strain of Penicillium raistrickii generated through thermo change. Mar Drugs 16:213
Luan Y, Wei H, Zhang Z, Che Q, Liu Y, Zhu T, Mandi A, Kurtan T, Gu Q, Li D (2014) Eleganketal a, a highly oxygenated dibenzospiroketal from the marine-derived fungus Spicaria elegans KLA03. J Nat Prod 77(7):1718–1723
Marmann A, Aly AH, Lin W, Wang B, Proksch P (2014) Co-cultivation a powerful emerging tool for enhancing the chemical diversity of microorganisms. Mar Drugs 12(2):1043–1065
Meng LH, Li XM, Lv CT, Huang CG, Wang BG (2014) Brocazines A-F, cytotoxic bisthiodiketopiperazine derivatives from Penicillium brocae MA-231, an endophytic fungus derived from the marine mangrove plant Avicennia marina. J Nat Prod 77(8):1921–1927
Meng LH, Liu Y, Li XM, Xu GM, Ji NY, Wang BG (2015a) Citrifelins a and B, citrinin adducts with a tetracyclic framework from cocultures of marine-derived isolates of Penicillium citrinum and Beauveria felina. J Nat Prod 78(9):2301–2305
Meng LH, Zhang P, Li XM, Wang BG (2015b) Penicibrocazines A-E, five new sulfide diketopiperazines from the marine-derived endophytic fungus Penicillium brocae. Mar Drugs 13(1):276–287
Meng LH, Li XM, Liu Y, Xu GM, Wang BG (2017) Antimicrobial alkaloids produced by the mangrove endophyte Penicillium brocae MA-231 using the OSMAC approach. RSC Adv 7(87):55026–55033
Moore JM, Bradshaw E, Seipke RF, Hutchings MI, McArthur M (2012) Use and discovery of chemical elicitors that stimulate biosynthetic gene clusters in Streptomyces bacteria. Methods Enzymol 517:367–385
Oh D-C, Kauffman CA, Jensen PR, Fenical W (2007) Induced production of emericellamides a and B from the marine-derived fungus Emericella sp in competing co-culture. J Nat Prod 70(4):515–520
Oikawa H, Murakami Y, Ichihara A (1992) Useful approach to find the plausible biosynthetic precursors of secondary metabolites using P-450 inhibitors-postulated intermediates of chaetoglobosin-A1. J Chem Soc Perkin Trans 1(21):2949–2953
Ola ARB, Thomy D, Lai D, Broetz-Oesterhelt H, Prolcsch P (2013) Inducing secondary metabolite production by the endophytic fungus Fusarium tricinctum through coculture with Bacillus subtilis. J Nat Prod 76(11):2094–2099
Overy DP, Zidorn C, Petersen BO, Duus JO, Dalsgaard PW, Larsen TO, Phipps RK (2005) Medium dependant production of corymbiferone a novel product from Penicillium hordei cultured on plant tissue agar. Tetrahedron Lett 46(18):3225–3228
Pan R, Bai X, Chen J, Zhang H, Wang H (2019) Exploring structural diversity of microbe secondary metabolites using OSMAC strategy: a literature review. Front Microbiol 10:294
Paranagama PA, Wijeratne EMK, Gunatilaka AAL (2007) Uncovering biosynthetic potential of plant-associated fungi: effect of culture conditions on metabolite production by Paraphaeosphaeria quadriseptata and Chaetomium chiversii. J Nat Prod 70(12):1939–1945
Peng XP, Wang Y, Liu PP, Hong K, Chen H, Yin X, Zhu WM (2011) Aromatic compounds from the halotolerant fungal strain of Wallemia sebi PXP-89 in a hypersaline medium. Arch Pharm Res 34(6):907–912
Peng J, Gao H, Zhang X, Wang S, Wu C, Gu Q, Guo P, Zhu T, Li D (2014) Psychrophilins E-H and versicotide C, cyclic peptides from the marine-derived fungus Aspergillus versicolor ZLN-60. J Nat Prod 77(10):2218–2223
Ramm S, Krawczyk B, Muehlenweg A, Poch A, Moesker E, Suessmuth RD (2017) A self-sacrificing N-methyltransferase is the precursor of the fungal natural product omphalotin. Angew Chem Int Ed 56(33):9994–9997
Rateb ME, Houssen WE, Harrison WTA, Deng H, Okoro CK, Asenjo JA, Andrews BA, Bull AT, Goodfellow M, Ebel R, Jaspars M (2011) Diverse metabolic profiles of a Streptomyces strain isolated from a hyper-arid environment. J Nat Prod 74(9):1965–1971
Ruiz B, Chavez A, Forero A, Garcia-Huante Y, Romero A, Sanchez M, Rocha D, Sanchez B, Rodriguez-Sanoja R, Sanchez S, Langley E (2010) Production of microbial secondary metabolites: regulation by the carbon source. Crit Rev Microbiol 36(2):146–167
Sato S (1990) Microbial production and control of cellular growth under high dissolved oxygen concentration. Hakkokogaku Kaishi 68(5):411–421
Scherlach K, Hertweck C (2009) Triggering cryptic natural product biosynthesis in microorganisms. Org Biomol Chem 7(9):1753–1760
Schneider P, Misiek M, Hoffmeister D (2008) In vivo and in vitro production options for fungal secondary metabolites. Mol Pharmaceut 5(2):234–242
Schroeckh V, Scherlach K, Nuetzmann HW, Shelest E, Schmidt-Heck W, Schuemann J, Martin K, Hertweck C, Brakhage AA (2009) Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans. Proc Natl Acad Sci 106(34):14558–14563
Senadeera SPD, Wiyakrutta S, Mahidol C, Ruchirawat S, Kittakoop P (2012) A novel tricyclic polyketide and its biosynthetic precursor azaphilone derivatives from the endophytic fungus Dothideomycete sp. Org Biomol Chem 10(35):7220–7226
Seyedsayamdost MR (2014) High-throughput platform for the discovery of elicitors of silent bacterial gene clusters. Proc Natl Acad Sci 111(20):7266–7271
Shang Z, Salim AA, Capon RJ (2017) Chaunopyran a: co-cultivation of marine mollusk-derived fungi activates a rare class of 2-alkenyl-tetrahydropyran. J Nat Prod 80(4):1167–1172
Singh V, Haque S, Niwas R, Srivastava A, Pasupuleti M, Tripathi CKM (2017) Strategies for fermentation medium optimization: an indepth review. Front Microbiol 7:2087
Singh G, Kumar A, Verma MK, Gupta P, Katoch M (2022) Secondary metabolites produced by Macrophomina phaseolina, a fungal root endophyte of Brugmansia aurea, using classical and epigenetic manipulation approach. Folia Microbiol 67(5):793–799
Siridechakorn I, Yue Z, Mittraphab Y, Lei X, Pudhom K (2017) Identification of spirobisnaphthalene derivatives with anti-tumor activities from the endophytic fungus Rhytidhysteron rufulum AS21B. Bioorg Med Chem 25(11):2878–2882
Sun J, Awakawa T, Noguchi H, Abe I (2012) Induced production of mycotoxins in an endophytic fungus from the medicinal plant Datura stramonium L. Bioorg Med Chem Lett 22(20):6397–6400
Sureram S, Wiyakrutta S, Ngamrojanavanich N, Mahidol C, Ruchirawat S, Kittakoop P (2012) Depsidones, aromatase inhibitors and radical scavenging agents from the marine-derived fungus Aspergillus unguis CRI282-03. Planta Med 78(6):582–588
Sureram S, Kesornpun C, Mahidol C, Ruchirawat S, Kittakoop P (2013) Directed biosynthesis through biohalogenation of secondary metabolites of the marine-derived fungus Aspergillus unguis. RSC Adv 3(6):1781–1788
Tammen SA, Friso S, Choi SW (2013) Epigenetics: the link between nature and nurture. Mol Asp Med 34(4):753–764
Tan YH, Wang ZX, Marshall KC (1998) Modeling pH effects on microbial growth: a statistical thermodynamic approach. Biotechnol Bioeng 59(6):724–731
Tang JW, Wang WG, Li A, Yan BC, Chen R, Li XN, Du X, Sun HD, Pu JX (2017) Polyketides from the endophytic fungus Phomopsis sp sh917 by using the one strain/many compounds strategy. Tetrahedron 73(26):3577–3584
Teles APC, Takahashi JA (2013) Paecilomide, a new acetylcholinesterase inhibitor from Paecilomyces lilacinus. Microbiol Res 168(4):204–210
Tran-Cong NM, Mandi A, Kurtan T, Muller WEG, Kalscheuer R, Lin W, Liu Z, Proksch P (2019) Induction of cryptic metabolites of the endophytic fungus Trichocladium sp. through OSMAC and co-cultivation. RSC Adv 9(47):27279–27288
Uchoa PKS, Pimenta ATA, Braz-Filho R, Oliveira MCF, Saraiva NN, Rodrigues BSF, Pfenning LH, Abreu LM, Wilke DV, Florenciog KGD, Lima MAS (2017) New cytotoxic furan from the marine sediment-derived fungi Aspergillus Niger. Nat Prod Res 31(22):2599–2603
Valente AMMP, Ferreira AG, Daolio C, Rodrigues FE, Boffo EF, Souza AQL, Sebastianes FLS, Melo IS (2013) Production of 5-hydroxy-7-methoxy-4-methylphthalide in a culture of Penicillium crustosum. An Acad Bras Cienc 85(2):487–496
Vervoort HC, Draskovic M, Crews P (2011) Histone deacetylase inhibitors as a tool to up-regulate new fungal biosynthetic products: isolation of EGM-556, a cyclodepsipeptide, from Microascus sp. Org Lett 13(3):410–413
Wakefield J, Hassan HM, Jaspars M, Ebel R, Rateb ME (2017) Dual induction of new microbial secondary metabolites by fungal bacterial co-cultivation. Front Microbiol 8:1284
Wang X, Sena JG, Hoover AR, King JB, Ellis TK, Powell DR, Cichewicz RH (2010) Chemical epigenetics alters the secondary metabolite composition of guttate excreted by an Atlantic-forest-soil-derived Penicillium citreonigrum. J Nat Prod 73(5):942–948
Wang FZ, Wei HJ, Zhu TJ, Li DH, Lin ZJ, Gu QQ (2011) Three new cytochalasins from the marine-derived fungus Spicaria elegans KLA03 by supplementing the cultures with L- and D-tryptophan. Chem Biodivers 8(5):887–894
Wang QX, Bao L, Yang XL, Guo H, Yang RN, Ren B, Zhang LX, Dai HQ, Guo LD, Liu HW (2012a) Polyketides with antimicrobial activity from the solid culture of an endolichenic fungus Ulocladium sp. Fitoterapia 83(1):209–214
Wang X, You J, King JB, Powell DR, Cichewicz RH (2012b) Waikialoid a suppresses hyphal morphogenesis and inhibits biofilm development in pathogenic Candida albicans. J Nat Prod 75(4):707–715
Wang QX, Bao L, Yang XL, Guo H, Ren B, Guo LD, Song FH, Wang WZ, Liu HW, Zhang LX (2013a) Tricycloalternarenes F-H: three new mixed terpenoids produced by an endolichenic fungus Ulocladium sp using OSMAC method. Fitoterapia 85:8–13
Wang QX, Bao L, Yang XL, Liu DL, Guo H, Dai HQ, Song FH, Zhang LX, Guo LD, Li SJ, Liu HW (2013b) Ophiobolins P-T, five new cytotoxic and antibacterial sesterterpenes from the endolichenic fungus Ulocladium sp. Fitoterapia 90:220–227
Wang JF, Xu FQ, Wang Z, Lu X, Wan JT, Yang B, Zhou XF, Zhang TY, Tu ZC, Liu Y (2014a) A new naphthalene glycoside from the sponge-derived fungus Arthrinium sp ZSDS1-F3. Nat Prod Res 28(14):1070–1074
Wang WJ, Li DY, Li YC, Hua HM, Ma EL, Li ZL (2014b) Caryophyllene sesquiterpenes from the marine-derived fungus Ascotricha sp ZJ-M-5 by the one strain-many compounds strategy. J Nat Prod 77(6):1367–1371
Wang B, Park EM, King JB, Mattes AO, Nimmo SL, Clendinen C, Edison AS, Anklin C, Cichewicz RH (2015a) Transferring fungi to a deuterium-enriched medium results in assorted, conditional changes in secondary metabolite production. J Nat Prod 78(6):1415–1421
Wang J, Wang Z, Ju Z, Wan J, Liao S, Lin X, Zhang T, Zhou X, Chen H, Tu Z, Liu Y (2015b) Cytotoxic cytochalasins from marine-derived fungus Arthrinium arundinis. Planta Med 81(2):160–166
Wang J, Wei X, Qin X, Lin X, Zhou X, Liao S, Yang B, Liu J, Tu Z, Liu Y (2015c) Arthpyrones A-C, Pyridone alkaloids from a sponge-derived fungus Arthrinium arundinis ZSDS1-F3. Org Lett 17(3):656–659
Wang L, Li M, Tang J, Li X (2016a) Eremophilane sesquiterpenes from a deep marine-derived fungus, Aspergillus sp SCSIOW2, cultivated in the presence of epigenetic modifying agents. Molecules 21(4):473
Wang M, Carver JJ, Phelan VV, Sanchez LM, Garg N, Peng Y, Don DN, Watrous J et al (2016b) Sharing and community curation of mass spectrometry data with global natural products social molecular networking. Nat Biotechnol 34(8):828–837
Wasil Z, Pahirulzaman KAK, Butts C, Simpson TJ, Lazarus CM, Cox RJ (2013) One pathway, many compounds: heterologous expression of a fungal biosynthetic pathway reveals its intrinsic potential for diversity. Chem Sci 4(10):3845–3856
Wijeratne EMK, Carbonezi CA, Takahashi JA, Seliga CJ, Turbyville TJ, Pierson EE, Pierson LS, VanEtten HD, Whitesell L, Bolzani VDS, Gunatilaka AAL (2004) Isolation, optimization of production and structure-activity relationship studies of monocillin I, the cytotoxic constituent of Paraphaeosphaeria quadriseptata. J Antibiot 57(8):541–546
Wijesekera K, Mahidol C, Ruchirawat S, Kittakoop P (2017) Metabolite diversification by cultivation of the endophytic fungus Dothideomycete sp. in halogen containing media: cultivation of terrestrial fungus in seawater. Bioorg Med Chem 25:2868–2877
Williams RB, Henrikson JC, Hoover AR, Lee AE, Cichewicz RH (2008) Epigenetic remodeling of the fungal secondary metabolome. Org Biomol Chem 6(11):1895–1897
Wu G, Sun X, Yu G, Wang W, Zhu T, Gu Q, Li D (2014) Cladosins A-E, hybrid polyketides from a deep-sea-derived fungus, Cladosporium sphaerospermum. J Nat Prod 77(2):270–275
Wu C, Zacchetti B, Ram AFJ, Wezel GP, Claessen D, Choi YH (2015) Expanding the chemical space for natural products by Aspergillus-Streptomyces co-cultivation and biotransformation. Sci Rep 5:10868
Xie LR, Li DY, Li ZL, Hua HM, Wang PL, Wu X (2013) A new cyclonerol derivative from a marine-derived fungus Ascotricha sp ZJ-M-5. Nat Prod Res 27(9):847–850
Xie CL, Liu Q, He ZH, Gai YB, Zou ZB, Shao ZZ, Liu GM, Chen HF, Yang XW (2021) Discovery of andrastones from the deep-sea-derived Penicillium allii-sativi MCCC 3A00580 by OSMAC strategy. Bioorg Chem 108:104671
Yamazaki H, Rotinsulu H, Narita R, Takahashi R, Namikoshi M (2015a) Induced production of halogenated epidithiodiketopiperazines by a marine-derived Trichoderma cf. brevicompactum with sodium halides. J Nat Prod 78(10):2319–2321
Yamazaki H, Takahashi O, Murakami K, Namikoshi M (2015b) Induced production of a new unprecedented epitrithiodiketopiperazine, chlorotrithiobrevamide, by a culture of the marine-derived Trichoderma cf. brevicompactum with dimethyl sulfoxide. Tetrahedron Lett 56(45):6262–6265
Yang XL, Li ZZ (2013) New spiral gamma-lactone enantiomers from the plant endophytic fungus Pestalotiopsis foedan. Molecules 18(2):2236–2242
Yang XL, Awakawa T, Wakimoto T, Abe I (2013) Induced production of novel prenyldepside and coumarins in endophytic fungi Pestalotiopsis acaciae. Tetrahedron Lett 54(43):5814–5817
Yang XL, Huang L, Ruan XL (2014) Epigenetic modifiers alter the secondary metabolite composition of a plant endophytic fungus, Pestalotiopsis crassiuscula obtained from the leaves of Fragaria chiloensis. J Asian Nat Prod Res 16(4):412–417
Yu GH, Wu GW, Zhu TJ, Gu QQ, Li DH (2015) Cladosins F and G, two new hybrid polyketides from the deep-sea-derived Cladosporium sphaerospermum 2005-01-E3. J Asian Nat Prod Res 17(2):120–124
Yuan C, Wang HY, Wu CS, Jiao Y, Li M, Wang YY, Wang SQ, Zhao ZT, Lou HX (2013) Austdiol, fulvic acid and citromycetin derivatives from an endolichenic fungus, Myxotrichum sp. Phytochem Lett 6(4):662–666
Yuan C, Guo YH, Wang HY, Ma XJ, Jiang T, Zhao JL, Zou ZM, Ding G (2016) Allelopathic polyketides from an endolichenic fungus Myxotrichum sp. by using OSMAC strategy. Sci Rep 6:19350
Zhang L, Niaz SI, Khan D, Wang Z, Zhu Y, Zhou H, Lin Y, Li J, Liu L (2017a) Induction of diverse bioactive secondary metabolites from the mangrove endophytic fungus Trichoderma sp (strain 307) by co-cultivation with Acinetobacter johnsonii (strain B2). Mar Drugs 15(2):35
Zhang Z, He X, Zhang G, Che Q, Zhu T, Gu Q, Li D (2017b) Inducing secondary metabolite production by combined culture of Talaromyces aculeatus and Penicillium variabile. J Nat Prod 80(12):3168–3172
Zhang H, Ruan C, Bai X, Chen J, Wang H (2018a) Heterocyclic alkaloids as antimicrobial agents of Aspergillus fumigatus D endophytic on Edgeworthia chrysantha. Chem Nat Compd 54(2):411–414
Zhang H, Zhao Z, Chen J, Bai X, Wang H (2018b) Tricycloalternarene aanalogs from a symbiotic fungus Aspergillus sp D and their antimicrobial and cytotoxic effects. Molecules 23(4):855–861
Zhao Q, Wang GQ, Chen GD, Hu D, Li XX, Guo LD, Li Y, Yao XS, Gao H (2015) Nodulisporisteroids C-L, new 4-methyl-progesteroid derivatives from Nodulisporium sp. Steroids 102:101–109
Zheng Y, Zhao B, Lu C, Lin X, Zheng Z, Su W (2009) Isolation, structure elucidation and apoptosis-inducing activity of new compounds from the edible fungus Lentinus striguellus. Nat Prod Commun 4(4):501–506
Zheng QC, Chen GD, Kong MZ, Li GQ, Cui JY, Li XX, Wu ZY, Guo LD, Cen YZ, Zheng YZ, Gao H (2013) Nodulisporisteriods a and B, the first 3,4-seco-4-methyl-progesteroids from Nodulisporium sp. Steroids 78:896–901
Zhu F, Chen G, Chen X, Huang M, Wan X (2011) Aspergicin, a new antibacterial alkaloid produced by mixed fermentation of two marine-derived mangrove epophytic fungi. Chem Nat Compd 47(5):767–769
Zuck KM, Shipley S, Newman DJ (2011) Induced production of N-formyl alkaloids from Aspergillus fumigatus by co-culture with Streptomyces peucetius. J Nat Prod 74(7):1653–1657
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2024 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Zhu, W., Zhang, H. (2024). Enhancing Chemical Diversity of Fungal Secondary Metabolite by OSMAC Strategy. In: Deshmukh, S.K., Takahashi, J.A., Saxena, S. (eds) Fungi Bioactive Metabolites. Springer, Singapore. https://doi.org/10.1007/978-981-99-5696-8_18
Download citation
DOI: https://doi.org/10.1007/978-981-99-5696-8_18
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-99-5695-1
Online ISBN: 978-981-99-5696-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)