State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Microbial Culture Collection Center (GDMCC), Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, 510070, People's Republic of China.
J Ind Microbiol Biotechnol. 2020 May;47(4-5):383-393. doi: 10.1007/s10295-020-02271-x. Epub 2020 Mar 31.
Metabolic engineering is usually focused on static control of microbial cell factories to efficient production of interested chemicals, though heterologous pathways compete with endogenous metabolism. However, products like carotenoids may cause metabolic burden on engineering strains, thus limiting product yields and influencing strain growth. Herein, a growth-phase-dependent regulation was developed to settle this matter, and its efficiency was verified using the heterogenous biosynthesis of lycopene in Saccharomyces cerevisiae as an example. Through growth-phase-dependent control of the lycopene biosynthetic pathway, limited step in MVA pathway, and competitive squalene pathway, production yield was increased by approximately 973-fold (from 0.034- to 33.1-mg/g CDW) and 1.48 g/L of production was obtained by one-stage fermentation in a 5-L bioreactor. Our study not only introduces an economically approach to the production of carotenoids, but also provides an example of dynamic regulation of biosynthetic pathways for metabolic engineering.
代谢工程通常侧重于通过静态控制微生物细胞工厂来高效生产感兴趣的化学品，尽管异源途径与内源性代谢竞争。然而，类胡萝卜素等产物可能会给工程菌株带来代谢负担，从而限制产物产量并影响菌株生长。本文开发了一种依赖于生长阶段的调控方法，并通过利用酿酒酵母中番茄红素的异源生物合成作为示例验证了其效率。通过依赖于生长阶段的调控番茄红素生物合成途径、甲羟戊酸途径中的限速步骤和竞争角鲨烯途径，可以将产量提高约 973 倍（从 0.034 至 33.1-mg/gCDW），并在 5-L 生物反应器中通过一级发酵获得 1.48g/L 的产物。我们的研究不仅为类胡萝卜素的生产提供了一种经济的方法，还为代谢工程中生物合成途径的动态调控提供了一个范例。
