Characterization of a Membrane-Bound O-Acetyltransferase Involved in Trioxacarcin Biosynthesis Offers Insights into Its Catalytic Mechanism  

作　　者：Yue Yin Yi Shen Song Meng Mei Zhang Hai-Xue Pan Gong-Li Tang 

机构地区：[1]State Key Laboratory of Bioorganic and Natural Products Chemistry,Center for Excellence in Molecular Synthesis,Shanghai Institute of Organic Chemistry,University of Chinese Academy of Sciences,Chinese Academy of Sciences,345 Lingling Road,Shanghai 200032,China [2]School of Chemistry and Material Sciences,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,1 Sub-lane Xiangshon,Hangzhou,Zhejiang 310024,China

出　　处：《Chinese Journal of Chemistry》2020年第12期1607-1611,共5页中国化学（英文版）

基　　金：We thank the supporting grants from the NNSFC(Nos.21632007 and 21621002);the CAS(No.XDB20000000 and K.c.wong Education Foundation).

摘　　要：of main observation and conclusion Trioxacarcin A(TXN-A)is a polycyclic aromatic natural product with remarkable biological activity.TxnB11,a membrane-bound O-acetyltransferase involved in TXN-A biosynthesis that is difficult for protein manipulation,is biochemically characterized here for its acetylation function on C4-sugar.A proposed catalytic mechanism is supported by transmembrane helix analysis and site-directed mutagenesis,in which four conserved amino acid residues His35,Ser71,His1OO and His317 are essential for enzyme activity.We tested the substrate tolerance of TxnB11 to acyl donors in vitro and found that TxnB11 can also utilize propionyl-CoA and glycolyl-CoA,resulting in two new TXN analogs with anti-tumor activity.This work provides a first understanding of the catalytic mechanism of this unusual acyltransferase family and presents good candidates for creating structural diversity for natural products.

关 键 词：utilize CATALYTIC ANALOGS 

分 类 号：O62[理学—有机化学]