Efficient 3-hydroxypropionic acid production from glycerol by metabolically engineered Klebsiella pneumoniae

Background: 3-Hydroxypropionic acid (3-HP) is one of the top value-added chemicals that can be produced from renewable resources. Crude glycerol, a cheap feedstock, is the foremost by-product generated from biodiesel industries. In this study, Klebsiella pneumonia was engineered for efficient 3-HP production from glycerol. Results: Three metabolically engineered K. pneumoniae strains were constructed and the strain JJQ02 (Delta ldhA Delta dhaT) overexpressing aldehyde dehydrogenase from E. coil was the most suitable for 3-HP production. This strain produced 61.9 g/L of 3-HP (a yield of 0.58 mol/mol) in 38 h in a 5-L fermentor by control of the aeration rate. Deletion of IdhA and dhaTeffectively eliminated lactate formation and reduced 1,3-propanediol production, but more 2,3-butanediol was accumulated due to redox balance. The fed-batch process was successfully scaled-up in a 300-L bioreactor where the 3-HP production level was 54.5 g/L (a yield of 0.43 mol/mol) in 51 h. Conclusions: Deficiency of both lactate dehydrogenase and 1,3-propanediol oxidoreductase as well as control of aeration significantly enhanced 3-HP production, and the successful scale-up of the fed-batch process in a 300-L bioreactor indicated a great potential to industrial production of 3-HP.