Metabolic Engineering of <i>Saccharomyces cerevisiae</i> for Vitamin B5 Production

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 <i>Saccharomyces cerevisiae</i>. 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 <i>S. cerevisiae</i>. By adjusting the copy number of the pathway modules, knocking out the endogenous bypass gene, balancing NADPH utilization, and regulating the <i>GAL</i> 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 <i>S. cerevisiae</i> to date. This study provides guidance for the development of vitamin B5 microbial cell factories.