Systems Metabolic Engineering of <i>Clostridium tyrobutyricum</i> for 1,3‐Propanediol Production From Crude Glycerol

Clostridium tyrobutyricum has emerged as a non-pathogenic microbial cell factory capable of anaerobic production of various value-added products, such as butyrate, butanol, and butyl butyrate. This study reports the first systematic engineering of C. tyrobutyricum for the heterologous production of 1,3-propanediol (1,3-PDO) from industrial by-product crude glycerol. Initially, the glycerol reductive pathway for 1,3-PDO production was constructed, and the unique glycerol oxidation pathway in C. tyrobutyricum was elucidated. Subsequently, the glycerol metabolism and 1,3-PDO synthesis pathways were enhanced. Furthermore, the intracellular reducing power supply and the fermentation process were optimized to improve 1,3-PDO production. Consequently, 54.06 g/L 1,3-PDO with a yield of 0.64 mol/mol and a productivity of 1.13 g/L·h was obtained using crude glycerol and fish meal. The strategies described herein could facilitate the engineering of C. tyrobutyricum as a robust host for synthesizing valuable chemicals.