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Discovery of a Potential Liver Fibrosis Inhibitor from a Mushroom Endophytic Fungus by Genome Mining of a Silent Biosynthetic Gene Cluster

文献类型：期刊论文

作者Cheng, Jin-Tao2,3,4; Wang, Han-Min5,6; Yu, Jia-Hui7; Sun, Chen-Fan2,3,4; Cao, Fei2,3,4; Jiang, Xin-Hang8; Chen, Xin-Ai2,3,4; Zhao, Qing-Wei2,3; Gan, Li-She7,9; Xie, Rong-Rong5
刊名JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
出版日期2021-09-29
卷号69期号:38页码:11303-11310
关键词fungus Calcarisporium arbuscula natural product gene cluster activation liver fibrosis
ISSN号0021-8561
DOI10.1021/acs.jafc.1c03639
通讯作者Zang, Yi(yzang@simm.ac.cn) ; Mao, Xu-Ming(xmmao@zju.edu.cn)
英文摘要Liver fibrosis has accounted for liver diseases and overall mortality, but no relevant drug has been developed. Filamentous fungi are important resources of natural products for pharmaceutical development. Calcarisporium arbuscula is a mushroom endophytic fungus, which primarily produces aurovertins. Here, in an aurovertin null-production mutant, one silent gene cluster (mcal7) was activated by overexpression of a pathway-specific zinc finger transcriptional regulator, and a tetramic acid-type compound (1, MCA17-1) was identified. Along with detailed structural characterization, its biosynthesis was proposed to be produced from the core PKS-NRPS hybrid enzyme. Moreover, 1 suppressed the activation of LX-2 upon transforming growth factor-beta (TGF-beta) challenge and had stronger bioactivity than the positive control obeticholic acid (OCA) against liver fibrosis. Our work suggested that this engineered fungus could be a producer of 1 for promising pharmaceutical development, and alternatively, it would be developed as a mushroom ingredient in dietary therapy to prevent liver fibrosis.
WOS关键词DRIVEN DISCOVERY ; POLYKETIDE ; METABOLITES ; ACTIVATION ; LEADS ; ACID
资助项目National Key R&D Program of China[2018YFA0903200] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program[2019ZX09201001-003-009] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program[2019ZX09201001-003-010] ; National Natural Science Foundation of China[31770071] ; National Natural Science Foundation of China[32070039]
WOS研究方向Agriculture ; Chemistry ; Food Science & Technology
语种英语
WOS记录号WOS:000704000600016
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/298347]  
专题新药研究国家重点实验室
通讯作者Zang, Yi; Mao, Xu-Ming
作者单位1.Zhejiang Shuren Univ, Hangzhou 310058, Peoples R China
2.Zhejiang Univ, Inst Pharmaceut Biotechnol, Affiliated Hosp 1, Sch Med, Hangzhou 310058, Zhejiang, Peoples R China
3.Zhejiang Univ, Res Ctr Clin Pharm, Affiliated Hosp 1, Sch Med, Hangzhou 310058, Zhejiang, Peoples R China
4.Zhejiang Prov Key Lab Microbial Biochem & Metab E, Hangzhou 310058, Peoples R China
5.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
7.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China
8.Zhejiang Univ, Coll Life Sci, Equipment & Technol Serv Platform, Hangzhou 310058, Peoples R China
9.Wuyi Univ, Sch Biotechnol & Hlth Sci, Jiangmen 529020, Guangdong, Peoples R China
10.Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China
推荐引用方式
GB/T 7714		 Cheng, Jin-Tao,Wang, Han-Min,Yu, Jia-Hui,et al. Discovery of a Potential Liver Fibrosis Inhibitor from a Mushroom Endophytic Fungus by Genome Mining of a Silent Biosynthetic Gene Cluster[J]. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,2021,69(38):11303-11310.
APA Cheng, Jin-Tao.,Wang, Han-Min.,Yu, Jia-Hui.,Sun, Chen-Fan.,Cao, Fei.,...&Mao, Xu-Ming.(2021).Discovery of a Potential Liver Fibrosis Inhibitor from a Mushroom Endophytic Fungus by Genome Mining of a Silent Biosynthetic Gene Cluster.JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,69(38),11303-11310.
MLA Cheng, Jin-Tao,et al."Discovery of a Potential Liver Fibrosis Inhibitor from a Mushroom Endophytic Fungus by Genome Mining of a Silent Biosynthetic Gene Cluster".JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 69.38(2021):11303-11310.

入库方式： OAI收割

来源：上海药物研究所

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