Genome Mining and Biosynthesis Study of a Type B Linaridin Reveals a Highly Versatileα-N-Methyltransferase  

作　　者：Fangting Wang Wanqing Wei Junfeng Zhao Tianlu Mo Xin Wang Xuedong Huang Suze Ma Shu Wang Zixin Deng Wei Ding Yong Liang Qi Zhang 

机构地区：[1]Department of Chemistry,Fudan University,Shanghai 200433 [2]State Key Laboratory of Coordination Chemistry,Jiangsu Key Laboratory of Advanced Organic Materials,Chemistry and Biomedicine Innovation Center,School of Chemistry and Chemical Engineering,Nanjing University,Nanjing 210023 [3]State Key Laboratory of Microbial Metabolism,School of Life Sciences&Biotechnology,Shanghai Jiao Tong University,Shanghai 200240

出　　处：《CCS Chemistry》2021年第3期1049-1057,共9页中国化学会会刊（英文）

基　　金：supported in part by grants from National Natural Science Foundation of China(21822703 and 31670060 to Q.Z.,21803030 to Y.L.,and 31600398 to W.D.);from the National Key Research and Development Program(2018Y F A0900402 and 2016 Y F A0501302);from Shanghai Key Laboratory of Bioactive Small Molecules(ZDSYS14005)。

摘　　要：Linaridins are a small but growing family of natural products belonging to the ribosomally synthesized and post-translationally modified peptide(RiPP)superfamily.In this study,a genome mining approach led to the identification of a novel linaridin,mononaridin(MON),from Streptomyces monomycini.In-frame deletion genetic knockout studies showed that,in addition to many genes essential for MON biosynthesis,monM encodes an S-adenosyl methionine(SAM)-dependentα-N-methyltransferase that is responsible for installing two methyl groups in the MON N-terminus.Besides SAM,MonM also accepts ethyl-SAM and allyl-SAM,in which the methyl of SAM is replaced by an ethyl and an allyl,respectively.We showed that ethyl-SAM and allyl-SAM have distinct reactivities in MonM catalysis,and this observation was further investigated in detail by density functional theory(DFT)calculations.Remarkably,MonM acts efficiently on nisin,a prototypic lantibiotic that is structurally very different from the native substrate,and the ability of MonM to transfer an allyl group to the nisin N-terminus allowed production of a fluorescently labeled nisin,which can be further used in microscopic cell analysis.Our studies provide new insights into linaridin biosynthesis and demonstrate the potential of linaridin methyltransferases in bioengineering applications.

关 键 词：substrate promiscuity SAM analogue dehydrobutyrine BIOSYNTHESIS lanthipeptide 

分 类 号：R318[医药卫生—生物医学工程]