文献类型：期刊文献

英文题名：Genome-guided investigation of anti-inflammatory sesterterpenoids with 5-15 trans-fused ring system from phytopathogenic fungi

作者：Jiang, Lan[1];Zhu, Guoliang[1];Han, Jianying[2,3];Hou, Chengjian[1];Zhang, Xue[1];Wang, Zhixin[1];Yuan, Weize[1];Lv, Kangjie[1];Cong, Zhanren[1];Wang, Xinye[1];Chen, Xiangyin[1];Karthik, Loganathan[1];Yang, Huanting[1];Wang, Xuyuan[1];Tan, Gaoyi[1];Liu, Guang[1];Zhao, Liya[4];Xia, Xuekui[4];Liu, Xiangyang[5];Gao, Shushan[2];Ma, Lei[6];Liu, Mei[2];Ren, Biao[7,8];Dai, Huanqin[9];Quinn, Ronald J.[3];Hsiang, Tom[10];Zhang, Jingyu[1];Zhang, Lixin[1];Liu, Xueting[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Key Lab Pathogen Microbiol & Immunol, Inst Microbiol, Beijing 100101, Peoples R China;[3]Griffith Univ, Griffith Inst Drug Discovery, Brisbane, Qld 4111, Australia;[4]Qilu Univ Technol, Biol Inst, Shandong Acad Sci, Jinan 250103, Shandong, Peoples R China;[5]T3 Biosci LLC, Milwaukee, WI 53211 USA;[6]East China Univ Sci & Technol, Shanghai Key Lab OfNew Drug Design, Sch Pharm, 130 Meilong Rd, Shanghai 200237, Peoples R China;[7]Sichuan Univ, State Key Lab Oral Dis, West China Hosp Stomatol, Chengdu 610041, Peoples R China;[8]Sichuan Univ, Natl Clin Res Ctr Oral Dis, West China Hosp Stomatol, Chengdu 610041, Peoples R China;[9]Chinese Acad Sci, State Key Lab Mycol, Inst Microbiol, Beijing 100101, Peoples R China;[10]Univ Guelph, Sch Environm Sci, Guelph, ON N1G 2W1, Canada

年份：2021

卷号：105

期号：13

起止页码：5407

外文期刊名：APPLIED MICROBIOLOGY AND BIOTECHNOLOGY

收录：;EI(收录号：20212610550626);WOS:【SCI-EXPANDED(收录号:WOS:000664007500001)】；

基金：We gratefully acknowledge the financial support from the National Key Research and Development Program of China (2019YFA0906200, 2020YFA090032, and 2020YFA0907200), the National Natural Science Foundation of China (21877038, 21907031, 81903529, 21977029, 31720103901, and 81573341), the Open Project Funding of the State Key Laboratory of Bioreactor Engineering, the 111 Project (B18022), Shanghai Rising-Star Program (20QA1402800), Shanghai Science and Technology Commission (18JC1411900). Genome sequencing and assembly of in-house genomes were supported by funding from the Natural Science and Engineering Research Council of Canada to T. Hsiang.

语种：英文

外文关键词：Fungi; Bifunctional terpene synthases; Terpenoids; Anti-inflammatory

摘要：Fungal terpenoids catalyzed by bifunctional terpene synthases (BFTSs) possess interesting bioactive and chemical properties. In this study, an integrated approach of genome mining, heterologous expression, and in vitro enzymatic activity assay was used, and these identified a unique BFTS sub-clade critical to the formation of a 5-15 trans-fused bicyclic sesterterpene preterpestacin I (1). The 5-15 bicyclic BFTS gene clusters were highly conserved but showed relatively wide phylogenetic distribution across several species of the diverged fungal classes Dothideomycetes and Sordariomycetes. Further genomic organization analysis of these homologous biosynthetic gene clusters from this clade revealed a glycosyltransferase from the graminaceous pathogen Bipolaris sorokiniana isolate BS11134, which was absent in other 5-15 bicyclic BFTS gene clusters. Targeted isolation guided by BFTS gene deletion led to the identification of two new sesterterpenoids (4, and 6) from BS11134. Compounds 2 and 4 showed moderate effects on LPS-induced nitrous oxide production in the murine macrophage-like cell line RAW264.7 with in vitro inhibition rates of 36.6 +/- 2.4% and 24.9 +/- 2.1% at 10 mu M, respectively. The plausible biosynthetic pathway of these identified compounds was proposed as well. This work revealed that phytopathogenic fungi can serve as important sources of active terpenoids via systematic analysis of the genomic organization of BFTS biosynthetic gene clusters, their phylogenetic distribution in fungi, and cyclization properties of their metabolic products.