Production of Industrial Chemicals from CO₂ by Engineering Cyanobacteria

As photosynthetic prokaryotes, cyanobacteria can directly convert CO₂ to organic compounds and grow rapidly using sunlight as the sole source of energy. The direct biosynthesis of chemicals from CO₂ and sunlight in cyanobacteria is therefore theoretically more attractive than using glucose as carbon source in heterotrophic bacteria. To date, more than 20 different target chemicals have been synthesized from CO₂ in cyanobacteria. However, the yield and productivity of the constructed strains is about 100-fold lower than what can be obtained using heterotrophic bacteria, and only a few products reached the gram level. The main bottleneck in optimizing cyanobacterial cell factories is the relative complexity of the metabolism of photoautotrophic bacteria. In heterotrophic bacteria, energy metabolism is integrated with the carbon metabolism, so that glucose can provide both energy and carbon for the synthesis of target chemicals. By contrast, the energy and carbon metabolism of cyanobacteria are separated. First, solar energy is converted into chemical energy and reducing power via the light reactions of photosynthesis. Subsequently, CO₂ is reduced to organic compounds using this chemical energy and reducing power. Finally, the reduced CO₂ provides the carbon source and chemical energy for the synthesis of target chemicals and cell growth. Consequently, the unique nature of the cyanobacterial energy and carbon metabolism determines the specific metabolic engineering strategies required for these organisms. In this chapter, we will describe the specific characteristics of cyanobacteria regarding their metabolism of carbon and energy, summarize and analyze the specific strategies for the production of chemicals in cyanobacteria, and propose metabolic engineering strategies which may be most suitable for cyanobacteria.