(S)-3-aminopiperidine-2,6-dione is a biosynthetic intermediate of microbial blue pigment indigoidine  

作　　者：Zhilong Zhang Pengwei Li Min Wang Yan Zhang Bian Wu Yong Tao Guohui Pan Yihua Chen 

机构地区：[1]State Key Laboratory of Microbial Resources,Institute of Microbiology,Chinese Academy of Sciences,Beijing,China [2]University of Chinese Academy of Sciences,Beijing,China [3]Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency,School of Pharmaceutical Science and Technology,Tianjin University,Tianjin,China

出　　处：《mLife》2022年第2期146-155,共10页微生物（英文）

基　　金：supported in part by the National Key R&D Program of China(2020YFA0907700);the NSFC grants(32025002 and 31522001).

摘　　要：The biosynthetic investigations of microbial natural products continuously provide powerful biocatalysts for the preparation of valuable chemicals.Practical methods for preparing(S)-3-aminopiperidine-2,6-dione(2),the pharmacophore of thalidomide(1)and its analog drugs,are highly desired.To develop a biocatalyst for producing(S)-2,we dissected the domain functions of IdgS,which is responsible for the biosynthesis of indigoidine(3),a microbial blue pigment that consists of two 2-like moieties.Our data supported that the L-glutamine tethered to the indigoidine assembly line is first offloaded and cyclized by the thioesterase domain to form(S)-2,which is then dehydrogenated by the oxidation(Ox)domain and finally dimerized to yield 3.Based on this,we developed an IdgS-derived enzyme biocatalyst,IdgS-Ox^(*)R539A,for preparing enantiomerically pure(S)-2.As a proof of concept,one-pot chemoenzymatic synthesis of 1 was achieved by combining the biocatalytic and chemical approaches.

关 键 词：(S)-3-aminopiperidine-2 6-dione BIOCATALYST blue pigment indigoidine THALIDOMIDE 

分 类 号：Q93[生物学—微生物学]