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
• 来源期刊: 中国化学（英文版）
• 年，卷（期）: 2020,（12）
• 所属期刊栏目: Concise Reports
• 页码范围: 1607-1611
• 页数: 5页
• 语种: 英文
• DOI: 10.1002/cjoc.202000284

摘要

Trioxacarcin A(TXN-A)is a polycyclic aromatic natural product with remarkable biological activity.TxnB11,a membrane-bbound O-acetyltransferase involved in TXN-A biosynthesis that is dificult 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 mutagene-sis,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 cre-ating structural diversity for natural products.