Metabolic engineering of cyanobacteria for photosynthetic 3-hydroxypropionic acid production from CO2 using...

Photosynthetic conversion of CO2 to chemicals using cyanobacteria is an attractive approach for direct recycling of CO2 to useful products. 3-Hydroxypropionic acid (3 HP) is a valuable chemical for the synthesis of polymers and serves as a precursor to many other chemicals such as acrylic acid. 3 HP is naturally produced through glycerol metabolism. However, cyanobacteria do not possess pathways for synthesizing glycerol and converting glycerol to 3 HP. Furthermore, the latter pathway requires coenzyme B12, or an oxygen sensitive, coenzyme B12-independent enzyme. These characteristics present major challenges for production of 3 HP using cyanobacteria. To overcome such difficulties, we constructed two alternative pathways in Synechococcus elongatus PCC 7942: a malonyl-CoA dependent pathway and a β-alanine dependent pathway. Expression of the malonyl-CoA dependent pathway genes (malonyl-CoA reductase and malonate semialdehyde reductase) enabled S. elongatus to synthesize 3 HP to a final titer of 665 mg/L. β-Alanine dependent pathway expressing S. elongatus produced 3H P to final titer of 186 mg/L. These results demonstrated the feasibility of converting CO2 into 3 HP using cyanobacteria.