Methylation in hangtaimycin biosynthesis and its antibacterial activities  

作　　者：Minghe Luo Yulu Dong Zixin Deng Yuhui Sun 

机构地区：[1]School of Pharmacy and Bioengineering,Chongqing University of Technology,Chongqing,China [2]Key Laboratory of Combinatorial Biosynthesis and Drug Discovery,Ministry of Education,and School of Pharmaceutical Sciences,Wuhan University,Wuhan,China

出　　处：《Synthetic and Systems Biotechnology》2023年第4期682-687,共6页合成和系统生物技术（英文）

基　　金：supported by National Key R&D Program of China(2018YFA0903200);General Program of National Natural Science Foundation of China(32370083);Natural Science Foundation of Chongqing CSTB(CSTB2022NSCQ-MSX0995);Graduate Innovation Program(GZLCX20232114)。

摘　　要：About two-thirds of small molecule drugs contain methyl group and it plays a very important role in the drug development.So,methyltransferases catalyzing the methylation have always attracted great attention.Hangtaimycin(HTM)is a potent hepatoprotective agent.Previous study showed that its biosynthetic gene cluster contained three methyltransferase domains,but their characteristics in HTM biosynthetic pathway has not been revealed.In this study,we clarified multi-methylations in HTM biosynthesis in vivo.It showed that the two S-adenosylmethionine-dependent methyltransferases(SAM-MTs)of HtmA2(-module 6)-MT domain and HtmB2(-module 18)-MT domain are responsible for the installation of methyl group at C-45 and N-12,respectively,whereas the FK506 methyltransferase(FKMT)type O-methyltransferase of HtmB1(-module 16)-MT domain take care of the methylation at O-21 of HTM.We also reported the antibacterial activities of HTM in this study,and found that it showed activities against M.luteus,B.thuringiensis and A.baumannii with MIC of 4μg/mL,4μg/mL,and 64μg/mL,respectively.

关 键 词：Hangtaimycin METHYLATION S-Adenosylmethionine-dependent METHYLTRANSFERASES FK506 methyltransferase type O-methyltransferase Antibacterial BIOSYNTHESIS 

分 类 号：R91[医药卫生—药学]