Thiamine Metabolism in Microbes and Strategies for Biomanufacturing.

Thiamine (Vitamin B1), an essential water-soluble vitamin, is composed of a pyrimidine and a thiazole ring. Owing to its functional roles as a coenzyme and its anti-inflammatory and antioxidant properties, it plays a critical role in disease prevention and therapeutic interventions. Currently, industrial production of thiamine relies primarily on chemical synthesis-a process that generates significant amounts of hazardous waste and byproducts. In contrast, microbial biosynthesis represents a more sustainable and environmentally friendly alternative. This review first outlines thiamine metabolism in microorganisms, highlighting ThiC as the key rate-limiting enzyme in its biosynthesis. It then summarizes potential strategies for improving thiamine biomanufacturing, and proposes that optimizing metabolic flux together with energy and cofactor balance at critical nodal points is essential for overcoming current yield limitations. Finally, to overcome specific bottlenecks in thiamine biosynthesis, such as precursor transport and pathway optimization, we propose that transport engineering and gene mining represent promising strategies complementary to recent advances in enzyme-directed evolution and metabolic engineering.