High-Performance Production of N-Acetyl-d-Neuraminic Acid with Whole Cells of Fast-Growing Vibrio natriegens via a Thermal Strategy

High performance is the core objective that biotechnologists pursue, of which low efficiency, low titer, and side products are the chief obstacles. Here, a thermal strategy is proposed for simultaneously addressing the obstacles of whole-cell catalysis that is widely applied in the food industry. The strategy, by combining fast-growing Vibrio natriegens, thermophilic enzymes, and high-temperature whole-cell catalysis, was successfully applied for the high-performance production of N-acetyl-d-neuraminic acid (Neu5Ac) that plays essential roles in the fields of food (infant formulas), healthcare, and medicine. By using this strategy, we realized the highest Neu5Ac titer and productivity of 126.1 g/L and up to 71.6 g/(L h), respectively, 7.2-fold higher than the productivity of Escherichia coli. The major byproduct acetic acid was also eliminated via quenching complex metabolic side reactions enabled by temperature elevation. This study offers a broadly applicable strategy for producing chemicals relevant to the food industry, providing insights for its future development.