L-xylulose, a new versatile rare sugar: recent biosynthetic advances and challenges

L-xylulose is a versatile L-form rare sugar with exceptional properties, including low caloric content, α-glucosidase inhibition, and antiviral effects, making it highly valuable for functional food and pharmaceutical applications. However, natural L-xylulose is extremely scarce, and its chemical synthesis is plagued by harsh conditions and isomer contamination, thus making biosynthesis-with its industrial potential and environmental friendliness-a promising alternative. This review summarizes the latest biosynthesis progress, analyzes six enzymatic pathways for L-xylulose and identifies two competitive routes, using xylitol and L-arabinitol as starting substrates. It further elaborates on core bottlenecks in chassis cell construction and industrial fermentation of L-xylulose, emphasizing that breakthroughs rely on three strategies: AI-driven high-yield strain screening, catalytic optimization of key enzymes, and efficient extracellular transport/secretion of the target product. Finally, the integration of synthetic biology with intelligent biomanufacturing is proposed as a crucial direction for efficient L-xylulose biosynthesis, facilitating its broader application across the food, pharmaceutical, and chemical industries.