Metabolic Engineering of <i>Saccharomyces cerevisiae</i> for Vitamin B5 Production
Jiaxuan Guo, Xixi Sun, Yu-Jie Yuan, Qitong Chen, Zutian Ou, Zixin Deng, Tian Ma, Tiangang Liu
Abstract
Vitamin B5, also called d -pantothenic acid, is an essential vitamin in the human body and is widely used in pharmaceuticals, nutritional supplements, food, and cosmetics. However, few studies have investigated the microbial production of d -pantothenic acid, especially in Saccharomyces cerevisiae . By employing a systematic optimization strategy, we screened seven key genes in d -pantothenic acid biosynthesis from diverse species, including bacteria, yeast, fungi, algae, plants, animals, etc., and constructed an efficient heterologous d -pantothenic acid pathway in S. cerevisiae . By adjusting the copy number of the pathway modules, knocking out the endogenous bypass gene, balancing NADPH utilization, and regulating the GAL inducible system, a high-yield d -pantothenic acid-producing strain, DPA171, which can regulate gene expression using glucose, was constructed. By optimizing fed-batch fermentation, DPA171 produced 4.1 g/L d -pantothenic acid, which is the highest titer in S. cerevisiae to date. This study provides guidance for the development of vitamin B5 microbial cell factories.