Coordination of metabolic pathways: Enhanced carbon conservation in 1,3-propanediol production by coupling with optically pure lactate biosynthesis

- Lactate was selected as the target co-product produced with 1,3-propanediol.
- By-product pathways were blocked in Klebsiella oxytoca PDL-0 for co-production.
- Lactate production balanced glycerol metabolism and drove 1,3-propanediol production.
- Over 70 g/L 1,3-propanediol and over 100 g/L optically pure lactate were produced.
- Total conversion yields of target products highly reached over 0.95 mol/mol, respectively.

Metabolic engineering has emerged as a powerful tool for bioproduction of both fine and bulk chemicals. The natural coordination among different metabolic pathways contributes to the complexity of metabolic modification, which hampers the development of biorefineries. Herein, the coordination between the oxidative and reductive branches of glycerol metabolism was rearranged in Klebsiella oxytoca to improve the 1,3-propanediol production. After deliberating on the product value, carbon conservation, redox balance, biological compatibility and downstream processing, the lactate-producing pathway was chosen for coupling with the 1,3-propanediol-producing pathway. Then, the other pathways of 2,3-butanediol, ethanol, acetate, and succinate were blocked in sequence, leading to improved d-lactate biosynthesis, which as return drove the 1,3-propanediol production. Meanwhile, efficient co-production of 1,3-propanediol and l-lactate was also achieved by replacing ldhD with ldhL from Bacillus coagulans. The engineered strains PDL-5 and PLL co-produced over 70 g/L 1,3-propanediol and over 100 g/L optically pure d-lactate and l-lactate, respectively, with high conversion yields of over 0.95 mol/mol from glycerol.