Engineering <i>Vibrio natriegens</i> as a Microbial Cell Factory for Efficient Xylitol Production from Nondetoxified and Nonsterilized Hemicellulose Hydrolysate

Vibrio natriegens (V. natriegens) is a highly promising and cost-effective next-generation microbial cell factory, which was first engineered here to successfully utilize hemicellulose hydrolysate for the production of xylitol, an important high-value compound. Systematic metabolic engineering strategies were employed in this study to enhance xylitol biosynthesis, including screening a highly efficient xylose reductase, constructing a heterologous xylitol synthesis pathway, analyzing and optimizing D-xylose transporters, reinforcing intracellular NADPH supply via cofactor engineering, and optimizing fermentation conditions. The resulting engineered strain achieved high-level xylitol production directly from nondetoxified and nonsterilized hemicellulose hydrolysate, reaching a titer of 60.06 g/L, yield of 1.01 g/g D-xylose, and a productivity of 1.15 g/L/h. To the best of our knowledge, this study reported the highest xylitol yield and productivity ever reported for microbial fermentation using nondetoxified and nonsterilized hemicellulose hydrolysate as the substrate. This study demonstrates the remarkable potential of engineered V. natriegens as a versatile microbial cell factory for diverse biochemicals.