Insufficient Acetyl-CoA Pool Restricts the Phototrophic Production of Organic Acids in Model Cyanobacteria.

Cyanobacteria are promising biological chassis to produce biochemicals such as carboxylic acids and their derivatives from CO2. In this manuscript, we reflected on cyanobacterial acetyl-CoA pool and TCA cycle as an important source of precursor molecules for the biosynthesis of carboxylic acids such as 3-hydroxypropionate, 3-hydroxybutyrate, succinate, malate, fumarate and free fatty acids, each of which is an important platform chemical for bioeconomy. We further highlighted specific features of the cyanobacterial TCA cycle, how it differs in structure and function from widely described TCA cycles of heterotrophic model organisms, and methods to make it more suitable for the production of carboxylic acids from CO2. Currently, the yields of these compounds are significantly lower than those in heterotrophic organisms and it was concluded that the primary cause of this can be attributed to the limited flux toward acetyl-CoA. Strategies like overexpressing pyruvate dehydrogenase complex or introducing synthetic bypasses are being explored to overcome these limitations. While significant progress has been made, further research is needed to enhance the metabolic efficiency of cyanobacteria, making them viable for the large-scale, sustainable production of carboxylic acids and their derivatives. [ABSTRACT FROM AUTHOR]