Systems metabolic engineering of Vibrio natriegens for the production of 1,3-propanediol

The economic viability of current bio-production systems is often limited by its low productivity due to slow cell growth and low substrate uptake rate. The fastest-growing bacterium Vibrio natriegens is a highly promising next-generation workhorse of the biotechnology industry which can utilize various industrially relevant carbon sources with high substrate uptake rates. Here, we demonstrate the first systematic engineering example of V. natriegens for the heterologous production of 1,3-propanediol (1,3-PDO) from glycerol. Systems metabolic engineering strategies have been applied in this study to develop a superior 1,3-PDO producer, including: (1) heterologous pathway construction and optimization; (2) engineering cellular transcriptional regulators and global transcriptomic analysis; (3) enhancing intracellular reducing power by cofactor engineering; (4) reducing the accumulation of toxic intermediate by pathway engineering; (5) systematic engineering of glycerol oxidation pathway to eliminate byproduct formation. A final engineered strain can efficiently produce 1,3-PDO with a titer of 56.2 g/L, a yield of 0.61 mol/mol, and an average productivity of 2.36 g/L/h. The strategies described in this study would be useful for engineering V. natriegens as a potential chassis for the production of other useful chemicals and biofuels. • Vibrio natriegens was engineered to produce 1,3-PDO from refined and crude glycerol. • Systems metabolic engineering strategies were combined to increase the production of 1,3-PDO. • Effect of arcA and glpR knockout was investigated by transcriptomics analysis. • The best strain can produce 1,3-PDO with a titer of 56.2 g/L, a yield of 0.61 mol/mol, and a productivity of 2.36 g/L/h.