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.
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)。
