Efficient 7-Dehydrocholesterol Production by Multiple Metabolic Engineering of Diploid Saccharomyces cerevisiae .

Autor: Ye Z; Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, Jiangsu 214122, China.; Science Center for Future Foods, Jiangnan University, Wuxi, Jiangsu 214122, China., Xu X; Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, Jiangsu 214122, China.; Science Center for Future Foods, Jiangnan University, Wuxi, Jiangsu 214122, China., Wu Y; Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, Jiangsu 214122, China.; Science Center for Future Foods, Jiangnan University, Wuxi, Jiangsu 214122, China., Liu Y; Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, Jiangsu 214122, China.; Science Center for Future Foods, Jiangnan University, Wuxi, Jiangsu 214122, China., Li J; Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, Jiangsu 214122, China.; Science Center for Future Foods, Jiangnan University, Wuxi, Jiangsu 214122, China., Du G; Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, Jiangsu 214122, China.; Science Center for Future Foods, Jiangnan University, Wuxi, Jiangsu 214122, China., Liu L; Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, Jiangsu 214122, China.; Science Center for Future Foods, Jiangnan University, Wuxi, Jiangsu 214122, China., Lv X; Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, Jiangsu 214122, China.; Science Center for Future Foods, Jiangnan University, Wuxi, Jiangsu 214122, China.
Jazyk: angličtina
Zdroj: Journal of agricultural and food chemistry [J Agric Food Chem] 2024 Nov 13; Vol. 72 (45), pp. 25186-25196. Date of Electronic Publication: 2024 Oct 31.
DOI: 10.1021/acs.jafc.4c07609
Abstrakt: 7-Dehydrocholesterol (7-DHC), a direct precursor of vitamin D3, has attracted increasing attention in microbial fermentation recently. In this study, 7-DHC biosynthesis in diploid Saccharomyces cerevisiae with robust ergosterol production was achieved by heterologous 24-dehydrocholesterol reductase expression, generating 44.1 mg/L 7-DHC, whereas the titer of ergosterol decreased by 40.5%. The ergosterol biosynthetic pathway was completely blocked by knocking out ERG6 and ERG5 , affording a 4.2-fold increase in the 7-DHC titer. Subsequently, the facilitation of the mevalonate and the postsqualene pathways accompanied by elimination of transcriptional repressors enhanced 7-DHC synthesis, and the 7-DHC titer reached 738.5 mg/L in a shake flask. Further validation in a 50 L fermenter demonstrated that the 7-DHC titer reached 3.80 g/L within just 24 h, with productivity reaching 158.3 mg/L/h, setting a new benchmark as the highest reported to date. This study paves the way toward a large-scale and cost-effective manufacture of 7-DHC.
Databáze: MEDLINE
Externí odkaz: