Metabolic Engineering of Saccharomyces cerevisiae for Vitamin B5 Production

• Published in: Journal of agricultural and food chemistry Vol. 71; no. 19; pp. 7408 - 7417
• Main Authors: Guo, Jiaxuan, Sun, Xixi, Yuan, Yujie, Chen, Qitong, Ou, Zutian, Deng, Zixin, Ma, Tian, Liu, Tiangang
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 17-05-2023
• Subjects: Bioactive Constituents, Metabolites, and Functions; Fermentation; Humans; Metabolic Engineering; Pantothenic Acid - genetics; Pantothenic Acid - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; d-pantothenic acid; vitamin B5; Saccharomyces cerevisiae; systematic metabolic engineering; fed-batch fermentation
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.3c01082

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.