Genetic Engineering Strategies for Enhancing Vitamin D3 Production in Saccharomyces cerevisiae Fermentation Systems

Vitamin D is a crucial fat-soluble vitamin that plays a significant role in maintaining human metabolism and normal physiological functions. Vitamin D3, one of the forms of vitamin D, exhibits high biological activity. Saccharomyces cerevisiae, a commonly used microbial host in bioengineering, offers numerous advantages and can serve as a chassis for fermentative production of vitamin D3. The synthesis of vitamin D3 begins with acetyl-CoA, a central carbon metabolism product. Acetyl-CoA proceeds through a series of biochemical reactions, including the mevalonate (MVA) pathway, the squalene pathway and the 7-dehydrocholesterol (7-DHC) pathway. These reactions ultimately yield 7-DHC, which is then converted to vitamin D3 under ultraviolet light irradiation. This process is regulated by various enzymes, such as the ERG series and DHCR24. This article summarizes several genetic engineering strategies to enhance 7-DHC production in Saccharomyces cerevisiae, including increasing the precursor metabolic flux, inhibiting the competing pathways, reconstructing the subcellular structures, and reducing the cytotoxicity of intermediates. These strategies hold significant potential for the industrial production of vitamin D3 and addressing global hidden hunger issues.