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. Industrial production of acetyl-CoA derivatives, especially commercial chemicals, depends on low feedstock costs.Enhancing acetyl-CoA synthesis from feedstocks such as glucose is essential for reducing the production costs of these end products.Reasonable use of carbon-saving pathways can maximize the production yield and rate of acetyl-CoA while lowering CO2 emission and oxygen dependency.The balance between reducing equivalents and energy must be well designed, especially for anaerobic processes.Fine-tuning the carbon flux between carbon-saving pathways and other pathways via metabolic engineering strategies is not only essential for redox and power balancing but also impels cells to fully utilize the feedstock to maximize the yield of acetyl-CoA and other end products.