司盈盈,冯庆梅
SI Yingying,FENG Qingmei

• 1:河南中医药大学药学院
• 2:河南省中药开发工程技术研究中心
• 3:河南中医药大学中医药科学院
• 4:豫产道地药材综合开发利用工程技术研究中心

摘要(Abstract)：

目的 对单菌多次级代谢产物(One strain many compounds, OSMAC)策略在微生物次级代谢产物研究中的应用进展进行综述。方法 查阅近年来的相关文献，对微生物次级代谢产物研究中所应用的OSMAC策略进行分类和归纳总结。结果 近年来所应用的OSMAC策略主要包括改变培养基、改变培养条件或培养状态、混合培养、化学表观遗传修饰、添加酶抑制剂或其他物质等。结论 OSMAC策略在激活微生物沉默基因、增加次级代谢产物多样性方面发挥了重要作用，随着现代科学技术的发展，OSMAC策略与新技术结合必然会成为发现新药和先导化合物的一条重要途径。
Objective To review the application of one strain many compounds(OSMAC) strategies in the study of microbial secondary metabolites.Methods The relevant literatures in recent years were searched, and the OSMAC strategies used in the study of microbial secondary metabolites were classified and summarized.Results The OSMAC strategies used in recent years mainly included changing culture medium, changing culture condition or culture state, mixed culture, chemical epigenetic modification, and adding enzyme inhibitors or other substances, etc.Conclusion OSMAC strategy plays an important role in activating microbial silent genes and increasing the diversity of secondary metabolites.With the development of modern science and technology, the combination of OSMAC strategy and new technology will inevitably become an important way to discover new drugs and lead compounds.

关键词(KeyWords)： OSMAC;单菌多次级代谢产物;沉默基因;微生物;次级代谢产物
OSMAC;one strain many compounds;silent gene;microbial;secondary metabolites

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 司盈盈,冯庆梅
SI Yingying,FENG Qingmei

DOI: 10.14066/j.cnki.cn21-1349/r.2021.0293

参考文献(References)：

• [1] WAISL Z,PAHIRULZAMAN K A K,BUTTS C,et al.One pathway,many compounds:heterologous expression of a fungal biosynthetic pathway reveals its intrinsic potential for diversity[J].Chem Sci,2013,4:3845-3856.
• [2] BODE H B,BETHE B,H?FS R,et a1.Big effects from small changes:possible ways to explore nature’s chemical diversity[J].ChemBioChem,2002,3(7):619-627.
• [3] ZHENG Q C,CHEN G D,KONG M Z,et al.Nodulisporisteriods A and B,the first 3,4-seco-4-methyl-progesteroids from Nodulisporium sp.[J].Steroids,2013,78(9):896-901.
• [4] ZHAO Q,WANG G Q,CHEN G D,et al.Nodulisporisteroids C-L,new 4-methyl-progesteroid derivatives from Nodulisporium sp.[J].Steroids,2015,102:101-109.
• [5] SENADEERA S P,WIYAKRUTTA S,MAHIDOL C,et al.A novel tricyclic polyketide and its biosynthetic precursor azaphilone derivatives from the endophytic fungus dothideomycete sp.[J].Org Biomol Chem,2012,10(35):7220-7226.
• [6] HEWAGE R T,AREE T,MAHIDOL C,et al.One strain-many compounds(OSMAC) method for production of polyketides,azaphilones,and an isochromanone using the endophytic fungus dothideomycete sp.[J].Phytochemistry,2014,108:87-94.
• [7] XU L L,CHEN H L,HAI P,et al.(+)- and(-)-Preuisolactone A:A pair of caged norsesquiterpenoidal enantiomers with a tricyclo[4.4.01,6.02,8]decane carbon skeleton from the endophytic fungus Preussia isomera[J].Org Lett,2019,21(4):1078-1081.
• [8] CHEN H L,ZHAO W T,LIU Q P,et al.(±)-Preisomide:A new alkaloid featuring a rare naturally occurring tetrahydro-2H-1,2-oxazin skeleton from an endophytic fungus Preussia isomera by using OSMAC strategy[J].Fitoterapia,2020,141:104475.
• [9] PARANAGAMA P A,KITHSIRI WIJERATNE E M,LESLIE GUNATILAKA A A.Uncovering biosynthetic potential of plant-associated fungi:Effect of culture conditions on metabolite production by Paraphaeosphaeria quadriseptata and Chaetofnium chiversii[J].J Nat Prod,2007,70(12):1939-1945.
• [10] WANG W J,LI D Y,LI Y C,et al.Caryophyllene sesquiterpenes from the marine-derived fungus Ascotricha sp.ZJ-M-5 by the one strain-many compounds strategy[J].J Nat Prod,2014,77(6):1367-1371.
• [11] FUCHSER J,THIERICKEB R,ZEECK A.Biosynthesis of aspinonene,a branched pentaketide produced by Aspergillus ochraceus,related to aspyrone[J].J Chem Soc,Perkin Trans 1,1995,1(13):1663-1666.
• [12] FUCHSER J,ZEECK A.Aspinolides and aspinonene/aspyrone co-metabolites,new pentaketides produced by Aspergillus ochraceus[J].Liebigs Annalen,1997,1:87-95.
• [13] SIRIDECHAKORN I,YUE Z W,MITTRAPHAB Y,et al.Identification of spirobisnaphthalene derivatives with anti-tumor activities from the endophytic fungus Rhytidhysteron rufulum AS21B[J].Bioorg Med Chem,2017,25(11):2878-2882.
• [14] NüTZMANN H W,REYES DOMINGUEZ Y,SCHERLACH K,et al.Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires saga/ada-mediated histone acetylation[J].P Natl Acad Sci USA,2011,108(34):14282-14287.
• [15] OLA A R B,THOMY D,LAI D,et al.Inducing secondary metabolite production by the endophytic fungus Fusarium tricinctum through coculture with Bacillus subtilis[J].J Nat Prod,2013,76(11):2094-2099.
• [16] EBRAHIM W,El NEKETI M,LEWALD L,et al.Metabolites from the fungal endophyte Aspergillus austroafricanus in axenic culture and in fungal-bacterial mixed cultures[J].J Nat Prod,2016,79(4):914-922.
• [17] KAMDEM R S T,WANG H,WAFO P,et al.Induction of new metabolites from the endophytic fungus Bionectria sp.through bacterial co-culture[J].Fitoterapia,2018,124:132-136.
• [18] LI C,SAROTTI A M,YANG B,et al.A new N-methoxypyridone from the co-cultivation of hawaiian endophytic fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062[J].Molecules,2017,22(7):1166-1173.
• [19] MANDELARE P E,ADPRESSA D A,KAWEESA E N,et al.Coculture of two developmental stages of a marine-derived Aspergillus alliaceus results in the production of the cytotoxic bianthrone Allianthrone A[J].J Nat Prod,2018,81(4):1014-1022.
• [20] STIERLE A A,STIERLE D B,DECATO D,et al.The berkeleylactones,antibiotic macrolides from fungal coculture[J].J Nat Prod,2017,80(4):1150-1160.
• [21] ZHANG W,CHEN M,SHAO C L,et al.The application of chemical epigenetic modification method in the research of secondary metabolites from fungi[J].Chinese Journal of Marine Drugs(中国海洋药物),2014,33(5):83-91.
• [22] MIAO F P,LIANG X R,LIU X H,et al.Aspewentins A-C,norditerpenes from a cryptic pathway in an algicolous strain of Aspergillus wentii[J].J Nat Prod,2014,77(2):429-432.
• [23] ASAI T,MORITA S,SHIRATA N,et al.Structural diversity of new C13-polyketides produced by Chaetomium mollipilium cultivated in the presence of a NAD+-dependent histone deacetylase inhibitor[J].Org Lett,2012,14(21):5456-5459.
• [24] ASAI T,YAMAMOTO T,OSHIMA Y.Histone deacetylase inhibitor induced the production of three novel prenylated tryptophan analogs in the entomopathogenic fungus,Torrubiella luteorostrata[J].Tetrahedron Lett,2011,52(52):7042-7045.
• [25] ASAI T,LUO D,OBARA Y,et al.Dihydrobenzofurans as cannabinoid receptor ligands from Cordyceps annullata,an entomopathogenic fungus cultivated in the presence of an HDAC inhibitor[J].Tetrahedron Lett,2012,53(17):2239-2243.
• [26] CHUNG Y M,WEI C K,CHUANG D W,et al.An epigenetic modifier enhances the production of anti-diabetic and anti-inflammatory sesquiterpenoids from Aspergillus sydowii[J].Bioorg Med Chem,2013,21(13):3866-3872.
• [27] YANG X L,HUANG L,RUAN X L.Epigenetic modifiers alter the secondary metabolite composition of a plant endophytic fungus,Pestalotiopsis crassiuscula obtained from the leaves of Fragaria chiloensis[J].J Asian Nat Prod Res,2014,16(4):412-417.
• [28] LIN Z J,ZHU T J,ZHANG G J,et al.Deoxy-cytochalasins from a marine-derived fungus Spicaria elegans[J].Canadian J Chem,2009,87(3):486-489.
• [29] WANG F Z,WEI H J,ZHU T J,et al.Three new cytochalasins from the marine-derived fungus Spicaria elegans KLA03 by supplementing the cultures with L- and D-tryptophan[J].Chem Biodivers,2011,8(5):887-894.
• [30] SI Y Y,TANG M X,LIN S,et al.Cytotoxic cytochalasans from Aspergillus flavipes PJ03-11 by OSMAC method[J].Tetrahedron Lett,2018,59(18):1767-1771.
• [31] LAURETI L,SONG L J,HUANG S,et al.Identification of a bioactive 51-membered macrolide complex by activation of a silent polyketide synthase in Streptomyces ambofaciens[J].P Natl Acad Sci,2011,108(15):6258-6263.
• [32] SIDDA J D,SONG L J,POON V,et al.Discovery of a family of γ-aminobutyrate ureas via rational derepression of a silent bacterial gene cluster[J].Chem Sci,2014,5(1):86-89.
• [33] ZHU M Z,CUI X L,LI M G,et al.A new approach for microbial drugs discovery:from genes to novel compounds[J].Natural Product Research and Development(天然产物研究与开发),2006,5(18):854-857.
• [34] WEI H J,LIN Z J,LI D H,et al.OSMAC(One Strain Many Compounds) approach in the research of microbial metabolites-A review[J].Acta Microbiologica Sinica(微生物学报),2010,50(6):701-709.
• [35] BANSKOTA A H,MCALPINE J B,SRENSEN D.Genomic analyses lead to novel secondary metabolites.part 3.ECO-0501,a novel antibacterial of a new class[J].J Antibiot,2006,59(9):533-542.
• [36] SCHERLACH K,HERTWECK C.Discovery of aspoquinolones A-D,prenylated quinoline-2-one alkaloids from Aspergillus nidulans,motivated by genome mining[J].Org Biomol Chem,2006,4(18):3517-3520.