Strategies for optimizing acetyl-CoA formation from glucose in bacteria.

Acetyl CoA is an important precursor for various chemicals. We provide a metabolic engineering guideline for the production of acetyl-CoA and other end products from a bacterial chassis. Among 13 pathways that produce acetyl-CoA from glucose, 11 lose carbon in the process, and two do not. The first 11 use the Embden-Meyerhof-Parnas (EMP) pathway to produce redox cofactors and gain or lose ATP. The other two pathways function via phosphoketolase with net consumption of ATP, so they must therefore be combined with one of the 11 glycolytic pathways or auxiliary pathways. Optimization of these pathways can maximize the theoretical acetyl-CoA yield, thereby minimizing the overall cost of subsequent acetyl-CoA-derived molecules. Other strategies for generating hyper-producer strains are also addressed.