Optimization of l -Fucose Biosynthesis in Escherichia coli through Pathway Engineering and Mixed Carbon Source Strategy

作者：Zihan Xia, Caiwen Lao, Jinyong Wu, Yiwen Jin, Xiangsong Chen, He Li, Xijie Fan, Lixia Yuan, Lijie Sun · 发表于：Journal of Agricultural and Food Chemistry · 年份：2025 · DOI：10.1021/acs.jafc.4c12544 · 被引用次数：10 · 研究领域：Infant Nutrition and Health、Pediatric Hepatobiliary Diseases and Treatments、Digestive system and related health

This study presents an engineered strain of Escherichia coli specifically designed to enhance the production of l -fucose while minimizing residues of 2′-fucosyllactose. The optimization strategies employed include the selection of key enzymes, optimization of gene copy numbers, and fermentation using mixed carbon sources. The metabolic flux was directed toward l -fucose synthesis by integrating preferred 1,2-fucosyltransferase and α- l -fucosidase into the genome. Furthermore, the gene copy numbers were optimized to enhance enzyme expression, thereby increasing l -fucose production. Additionally, the supply of guanosine 5′-triphosphate was improved, and cofactors were regenerated to better regulate metabolism. Modifications to transporter proteins effectively reduced the accumulation of 2′-fucosyllactose. The implementation of a glucose/glycerol co-fermentation strategy enhanced carbon flux distribution and strain efficiency. The optimized strain achieved a yield of 91.90 g/L of l -fucose in a 5 L bioreactor, representing an 80.01% increase over previous yields, with a productivity of 1.18 g L –1 h –1 . This yield is the highest reported for l -fucose, demonstrating its potential for industrial production.