Reprograming the Carbon Metabolism of Yeast for Hyperproducing Mevalonate, a Building Precursor of the Terpenoid Backbone

• Published in: Journal of agricultural and food chemistry 2024-12
• Main Authors: Zhang, Ge, Ma, Yurui, Huang, Meina, Jia, Kaizhi, Ma, Ting, Dai, Zongjie, Wang, Qinhong
• Format: Article
• Language: English
• ISSN: 1520-5118; 1520-5118
• DOI: 10.1021/acs.jafc.4c09874

Utilization of microbial hosts to produce natural plant products is regarded as a promising and sustainable approach. However, achieving highly efficient production of terpenoids using microorganisms remains a significant challenge. Here, mevalonate, a building block of terpenoids, was used as a demo product to explore the potential metabolic constraints for terpenoid biosynthesis in . First, by regulation of the expression of and , the mevalonate titer was improved by 7660%. Subsequently, the native mevalonate pathway (MVA pathway) was enhanced, and the production of mevalonate increased to 4.16 g/L. To ensure a sufficient supply of acetyl-CoA, the citrate route and TCA cycle were simultaneously engineered, and the mevalonate titer was further improved to 5.25 g/L in shake flasks. Ultimately, the citrate overflow metabolism of was eliminated by deleting , resulting in the highest mevalonate titer of 101 g/L with a yield of 0.255 g/g of glucose in eukaryotes. These insights could be applied to the effective production of terpenoids and biochemicals derived from central carbon metabolic pathways.