Methylation in hangtaimycin biosynthesis and its antibacterial activities
作者机构:School of Pharmacy and BioengineeringChongqing University of TechnologyChongqingChina Key Laboratory of Combinatorial Biosynthesis and Drug DiscoveryMinistry of Educationand School of Pharmaceutical SciencesWuhan UniversityWuhanChina
出 版 物:《Synthetic and Systems Biotechnology》 (合成和系统生物技术(英文))
年 卷 期:2023年第8卷第4期
页 面:682-687页
核心收录:
学科分类:1007[医学-药学(可授医学、理学学位)] 10[医学]
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)
主 题:Hangtaimycin Methylation S-Adenosylmethionine-dependent methyltransferases FK506 methyltransferase type O-methyltransferase Antibacterial Biosynthesis
摘 要:About two-thirds of small molecule drugs contain methyl group and it plays a very important role in the drug ***,methyltransferases catalyzing the methylation have always attracted great ***(HTM)is a potent hepatoprotective *** study showed that its biosynthetic gene cluster contained three methyltransferase domains,but their characteristics in HTM biosynthetic pathway has not been *** this study,we clarified multi-methylations in HTM biosynthesis in *** 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 *** also reported the antibacterial activities of HTM in this study,and found that it showed activities against ***,*** and *** with MIC of 4μg/mL,4μg/mL,and 64μg/mL,respectively.