文献类型：期刊文献

英文题名：Genome Mining Guided Discovery of Macrocyclic Sesterterpenoids with Anti-MRSA and Anti-Neuroinflammatory Activities

作者：Lan, Keying[1];Wang, Zhennan[1];Lv, Kangjie[1];Xing, Cuiping[1];Li, Xiaoying[1];Yin, Qiang[1];Chen, Yuwei[2];Mo, Xuming[3,4];Mao, Xiaobo[5];Wu, Weijie[6];Hsiang, Tom[7];Zhang, Lixin[1];Dai, Huanqin[8];Liu, Xueting[1];Zhu, Guoliang[1];Jiang, Lan[3,5]

机构：[1]East China Univ Sci Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Nanjing Tech Univ, Coll Biotechnol & Pharmaceut Engn, Nanjing 211816, Peoples R China;[3]Nanjing Med Univ, Childrens Hosp, Dept Cardiothorac Surg, Nanjing 210093, Peoples R China;[4]Nanjing Med Univ, State Key Lab Reprod Med & Offspring Hlth, Nanjing 210093, Peoples R China;[5]Johns Hopkins Univ, Inst Cell Engn, Neuroregenerat & Stem Cell Programs, Sch Med, Baltimore, MD 21205 USA;[6]Jiangsu Alphay Biotechnol Co Ltd, Nantong 226009, Peoples R China;[7]Univ Guelph, Sch Environm Sci, Guelph, ON N1G 2W1, Canada;[8]Chinese Acad Sci, Inst Microbiol, Chinese Acad Sci Key Lab Pathogen Microbiol & Immu, Beijing 100101, Peoples R China

年份：2025

卷号：73

期号：51

起止页码：32674

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20255219796110);WOS:【SCI-EXPANDED(收录号:WOS:001639313300001)】；

基金：We sincerely thank Prof. Hideaki Oikawa at Hokkaido University for his kind support of our project. And the support of Natural Science and Engineering Research Council of Canada to Prof. T. Hsiang, which funded the genome sequencing and assembly of C. cereale 00173.

语种：英文

外文关键词：bifunctional terpene synthases; macrocyclic sesterterpenoids; heterologous expression; biosynthetic pathway; antibacterial activity

摘要：Terpenoids exhibit antioxidant, antimicrobial, and health-promoting activities, and are widely utilized in the food industry. In this study, a new bifunctional terpene synthase (BFTPS) and its associated gene cluster were identified in Colletotrichum cereale 00173 through a genome mining approach. Heterologous expression of the BFTPS and its gene cluster in Aspergillus oryzae NSAR1 led to the production of a 14-membered macrocyclic sesterterpene, colcerepene (1), and four hydroxylated derivatives, colcerepenoids A-D (2-5). The biosynthetic pathway of compounds 1-5 was further elucidated through feeding experiments. Notably, compound 1 exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with an MIC value of 6.25 mu M. This study is the first report of anti-MRSA activity in macrocyclic sesterterpenoids, expanding the functional space of macrocyclic sesterterpenoids as promising leads for developing agents against foodborne pathogens.