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

IF 4.5 Q1 MICROBIOLOGY

mLife Pub Date : 2022-06-21 eCollection Date: 2022-06-01 DOI:10.1002/mlf2.12023

Zhilong Zhang, Pengwei Li, Min Wang, Yan Zhang, Bian Wu, Yong Tao, Guohui Pan, Yihua Chen

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Abstract

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.

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(S)-3-氨基哌啶-2,6-二酮是微生物蓝色素靛蓝的生物合成中间体。

微生物天然产物的生物合成研究不断为制备有价值的化学品提供强大的生物催化剂。制备(S)-3-氨基哌啶-2,6-二酮(2)（沙利度胺(1)及其类似药物的药本）的实用方法非常值得期待。为了开发生产(S)-2 的生物催化剂，我们对 IdgS 的结构域功能进行了剖析，IdgS 负责靛红素 (3) 的生物合成，靛红素是一种由两个类似 2 的分子组成的微生物蓝色色素。我们的数据证明，靛红素组装线上的 L-谷氨酰胺首先被硫酯酶结构域卸载和环化，形成 (S)-2，然后被氧化（Ox）结构域脱氢，最后二聚生成 3。在此基础上，我们开发了一种 IdgS 衍生酶生物催化剂 IdgS-Ox* R539A，用于制备对映体纯的 (S)-2。作为概念验证，我们结合生物催化和化学方法，实现了 1 的一锅化学合成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

mLife

CiteScore

2.30

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0.00%

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