Zhilong Zhang, Pengwei Li, Min Wang, Yan Zhang, Bian Wu, Yong Tao, Guohui Pan, Yihua Chen
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(S)-3-aminopiperidine-2,6-dione is a biosynthetic intermediate of microbial blue pigment indigoidine.
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.
期刊介绍:
Gastrointestinal Endoscopy is a journal publishing original, peer-reviewed articles on endoscopic procedures for studying, diagnosing, and treating digestive diseases. It covers outcomes research, prospective studies, and controlled trials of new endoscopic instruments and treatment methods. The online features include full-text articles, video and audio clips, and MEDLINE links. The journal serves as an international forum for the latest developments in the specialty, offering challenging reports from authorities worldwide. It also publishes abstracts of significant articles from other clinical publications, accompanied by expert commentaries.