Cyanobacterial photo-driven mixotrophic metabolism and its advantages for biosynthesis

Cyanobacterium offers a promising chassis for phototrophic production of renewable chemicals. Although engineered cyanobacteria can achieve similar product carbon yields as heterotrophic microbial hosts, their production rate and titer under photoautotrophic conditions are 10 to 100 folds lower than those in fast growing E. coli. Cyanobacterial factories face three indomitable bottlenecks. First, photosynthesis has limited ATP and NADPH generation rates. Second, CO₂ fixation by ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) has poor efficiency. Third, CO₂ mass transfer and light supply are deficient within large photobioreactors. On the other hand, cyanobacteria may employ organic substrates to promote phototrophic cell growth, N₂ fixation, and metabolite synthesis. The photo-fermentations show enhanced photosynthesis, while CO₂ loss from organic substrate degradation can be reused by the Calvin cycle. In addition, the plasticity of cyanobacterial pathways (e.g., oxidative pentose phosphate pathway and the TCA cycle) has been recently revealed to facilitate the catabolism. The use of cyanobacteria as “green E. coli” could be a promising route to develop robust photobiorefineries.[Figure not available: see fulltext.]