Advances in microbial cell factories for substitute sugar xylitol production: from metabolic engineering to AI-driven bioprocessing.

UNLABELLED: With the growing diabetic population, the substitute sweetener xylitol has attracted increasing attention. In this paper, advanced metabolic engineering strategies for food-grade xylitol production are summarized. This paper comprehensively analyzes core approaches, including metabolic pathway reconstruction, cofactor engineering, and the optimization of industrial chassis cells, to overcome significant enzymatic bottlenecks and carbon flux imbalances. Cutting-edge integration of artificial intelligence (AI) in predicting metabolic networks and guiding directed enzyme evolution is further highlighted, establishing a closed-loop "design-build-test-learn" framework. Coupled with techno-economic and sustainability analyses, this work evaluates the industrial feasibility and market competitiveness of bio-xylitol. Ultimately, this review provides a comprehensive blueprint for developing next-generation, cost-effective microbial cell factories. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-05072-8.