Metabolic Engineering of Saccharomyces cerevisiae for High-Level Production of Chlorogenic Acid from Glucose.
Metabolic Engineering of Saccharomyces cerevisiae for High-Level Production of Chlorogenic Acid from Glucose.
复制标题
DOI：
10.1021/acssynbio.1c00487
复制
发表时间：
2022-02
影响因子：
4.7
通讯作者：
F. Xiao;J. Lian;Shuai Tu;Linlin Xie;Jun Li;Fuming Zhang;R. Linhardt;Haichan Huang;Weihong Zh
中科院分区：
文献类型：
--
作者：
F. Xiao;J. Lian;Shuai Tu;Linlin Xie;Jun Li;Fuming Zhang;R. Linhardt;Haichan Huang;Weihong Zh
Chlorogenic acid (CGA), a major dietary phenolic compound, has been increasingly used in the food and pharmaceutical industries because of its ready availability and extensive biological and pharmacological activities. Traditionally, extraction from plants has been the main approach for the commercial production of CGA. This study reports the first efficient microbial production of CGA by engineering the yeast, Saccharomyces cerevisiae, on a simple mineral medium. First, an optimized de novo biosynthetic pathway for CGA was reconstructed in S. cerevisiae from glucose with a CGA titer of 36.6 ± 2.4 mg/L. Then, a multimodule engineering strategy was employed to improve CGA production: (1) unlocking the shikimate pathway and optimizing carbon distribution; (2) optimizing the l-Phe branch and pathway balancing; and (3) increasing the copy number of CGA pathway genes. The combination of these interventions resulted in an about 6.4-fold improvement of CGA titer up to 234.8 ± 11.1 mg/L in shake flask cultures. CGA titers of 806.8 ± 1.7 mg/L were achieved in a 1 L fed-batch fermenter. This study opens a route to effectively produce CGA from glucose in S. cerevisiae and establishes a platform for the biosynthesis of CGA-derived value-added metabolites.
