Metabolic engineering of cyanobacteria for photosynthetic 3-hydroxypropionic acid production from CO₂ using Synechococcus elongatus PCC 7942

Photosynthetic conversion of CO₂ to chemicals using cyanobacteria is an attractive approach for direct recycling of CO₂ to useful products. 3-Hydroxypropionic acid (3HP) is a valuable chemical for the synthesis of polymers and serves as a precursor to many other chemicals such as acrylic acid. 3HP is naturally produced through glycerol metabolism. However, cyanobacteria do not possess pathways for synthesizing glycerol and converting glycerol to 3HP. Furthermore, the latter pathway requires coenzyme B12, or an oxygen sensitive, coenzyme B12-independent enzyme. These characteristics present major challenges for production of 3HP 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 3HP to a final titer of 665mg/L. β-Alanine dependent pathway expressing S. elongatus produced 3HP to final titer of 186mg/L. These results demonstrated the feasibility of converting CO₂ into 3HP using cyanobacteria.