代谢工程调控策略在生物合成氨基酸及其衍生物中的应用

Metabolic engineering strategies in biosynthesis of amino acids and their derivatives

氨基酸的工业化生产已有上百年历史,多用于动物饲料和食品添加剂;很多种类的氨基酸如L-半胱氨酸、β-丙氨酸、S-腺苷甲硫氨酸、4-羟基异亮氨酸和高丝氨酸等也具有很高的应用价值。相较于化工合成或分离提取的方式,利用微生物细胞作为平台生产氨基酸及其衍生物具有绿色安全、可持续等独特的优势。本文综述了近年来微生物合成氨基酸及其衍生物的研究进展,分别介绍了碳源的高效利用、限速步骤的调节、碳通量的调节、转录和反馈抑制调节以及转运调节等代谢调控策略在提高微生物生产氨基酸及其衍生物效率的研究及应用,分析了不同调控策略的优势和缺点,总结了不同氨基酸及其衍生物的应用价值,最后展望了微生物作为细胞工厂生产各类氨基酸及其衍生物的广阔前景。

The industrial production of amino acids has a history of more than 100 years,and is mostly used in animal feed and food additives.Many types of amino acids such as L-cysteine,β-alanine,S-adenosylmethionine,4-hydroxyisocyanine acid and homoserine also have broad applications.Plant extraction and chemical synthesis are the commonly used methods to produce these amino acids and their derivatives.Compared with the way of chemical synthesis or separation and extraction,the use of microbial cells as a platform for the production of amino acids and derivatives has unique advantages such as green safety and sustainability.This review highlights the recent advances in developing metabolic engineering strategies including increase of the carbon sources uptake rate,elimination of the rate-limiting steps,enhancement of the carbon flux through the target pathway,remove of the feed-back inhibition effect and regulation of the intermediates and products transportation for biological production of amino acids and their derivatives.Our goals are to provide a landscape of current works and present guidelines to address future challenges in biosynthesis of amino acids and their derivatives using engineered microorganisms.