Directed Synthesis of Biobased 1,6-Diaminohexane from Adipic Acid by Rational Regulation of a Functional Enzyme Cascade in Escherichia coli
Directed Synthesis of Biobased 1,6-Diaminohexane from Adipic Acid by Rational Regulation of a Functional Enzyme Cascade in Escherichia coli
复制标题
DOI：
10.1021/acssuschemeng.3c00275
复制
发表时间：
2023-04
期刊：
影响因子：
--
通讯作者：
Li Wang;Guohui Li;Aitao Li;Yu Deng
中科院分区：
文献类型：
--
作者：
Li Wang;Guohui Li;Aitao Li;Yu Deng
一些酶在催化具有相似化学键的底物时具有相对特异性，从而允许一个酶参与多个反应。这种相对特异性给靶产物的合成带来了很大的挑战，特别是在全细胞系统中。本研究在大肠杆菌中构建了一个重定向羧酸还原酶级联，用于生物合成工程塑料单体1,6-二氨基己烷。采用一系列策略来指导1,6-二氨基己烷的生物合成，包括酶组分的挖掘、级联模块的设计、适应性分析和评价以及辅酶元件的调控，而不需要对酶进行任何定向突变以改变其特异性。1,6-二氨基己烷滴度为238.5 mg·L-1，比初始菌株提高了567倍。人工途径被证明对中链二胺是通用的，显示了关键元件自适应组装的能力，以重定向通量以生产目标。
Some enzymes are relatively specific when catalyzing substrates with similar chemical bonds, allowing a single enzyme to participate in multiple reactions. Such relative specificity brings great challenges to the synthesis of target products, especially in a whole-cell system. In this study, a redirected carboxylic acid reductase cascade was constructed inEscherichia colifor biosynthesis of the engineering plastics monomer 1,6-diaminohexane. A series of strategies were adopted to direct the biosynthesis of 1,6-diaminohexane, including mining of enzyme components, design of a cascade module, adaptation analysis and evaluation, and regulation of coenzyme elements, without any directed mutation of enzymes to change their specificity. The titer of 1,6-diaminohexane was increased 567-fold relative to the initial strain to 238.5 mg·L–1. The artificial pathway was proven to be universal for medium-chain diamines, showing the power of adaptive assembly of key elements to redirect flux for target production.