Substrate specificity and reaction directionality of a three-residue cyclophane forming enzyme Pau B  

作　　者：Yuanjun Han Suze Ma Qi Zhang 

机构地区：[1]Department of Chemistry,Fudan University,Shanghai 200433,China

出　　处：《Chinese Chemical Letters》2023年第1期362-366,共5页中国化学快报（英文版）

基　　金：supported by grants from the National Key Research and Development Program (Nos. 2018YFA0900402 and 2021YFA0910501);the National Natural Science Foundation of China (Nos. 21822703, 21921003, and 32070050);the funding of Innovative research team of high-level local universities in Shanghai;a key laboratory program of the Education Commission of Shanghai Municipality (No. ZDSYS14005);West Light Foundation of the Chinese Academy of Sciences (No. xbzgzdsys-202105)。

摘　　要：Three-residue cyclophane-forming enzymes(3-Cy FEs) are a group of radical S-adenosylmethionine(SAM)enzymes involved in the biosynthesis of ribosomally synthesized and posttranslationally modified peptides(Ri PPs). 3-Cy FE catalyzes the crosslinking between an aromatic residue(Ω1) and a non-aromatic residue(X3) in a Ω1-X2-X3 motif to produce a cyclophane ring, a key step in the biosynthesis of the Ri PP natural product triceptide. In this study, we perform a genome-wide search for the Xye-type triceptides, showing these Ri PPs are likely class-specific and only present in gamma-proteobacteria. The 3-Cy FE Pau B from Photorhabdus australis exhibits a relaxed substrate specificity on the X3 position, but glycine in this position is not suitable for cyclophane formation. We also reconstituted the activity of Pau B in vitro,showing it produces the N-terminal cyclophane firstly, and then the C-terminal ring, whereas the middle cyclophane is produced in the last step.

关 键 词：CYCLOPHANE BIOSYNTHESIS Radical SAM Enzyme catalysis Peptide Natural product 

分 类 号：O62[理学—有机化学]