Abstract
For an economically competitive biological process, achieving high carbon yield of a target chemical is crucial. In biochemical production, pyruvate and acetyl-CoA are primary building blocks. When sugar is used as the sole biosynthetic substrate, acetyl-CoA is commonly generated by pyruvate decarboxylation. However, pyruvate decarboxylation during acetyl-CoA formation limits the theoretical maximum carbon yield (TMCY) by releasing carbon, and in some cases also leads to redox imbalance. To avoid these problems, we describe here the construction of a metabolic pathway that simultaneously utilizes glucose and acetate. Acetate is utilized to produce acetyl-CoA without carbon loss or redox imbalance. We demonstrate the utility of this approach for isobutyl acetate (IBA) production, wherein IBA production with glucose and acetate achieves a higher carbon yield than with either sole carbon source. These results highlight the potential for this multiple carbon source approach to improve the TMCY and balance redox in biosynthetic pathways.
Highlights
For an economically competitive biological process, achieving high carbon yield of a target chemical is crucial
isobutyl acetate (IBA) production requires two moieties: isobutanol and acetyl-CoA; isobutanol can be effectively synthesized from two molecules of pyruvate with the aid of five enzymes (AlsS, IlvCD, Kivd and AdhA) in E. coli (Fig. 1)[26]
We constructed an efficient acetate-assimilating pathway (AckA–Pta pathway) in E. coli and demonstrated that the pathway is useful for E. coli growth and IBA production at high acetate concentrations
Summary
For an economically competitive biological process, achieving high carbon yield of a target chemical is crucial. Pyruvate decarboxylation during acetyl-CoA formation limits the theoretical maximum carbon yield (TMCY) by releasing carbon, and in some cases leads to redox imbalance. To avoid these problems, we describe here the construction of a metabolic pathway that simultaneously utilizes glucose and acetate. We demonstrate the utility of this approach for isobutyl acetate (IBA) production, wherein IBA production with glucose and acetate achieves a higher carbon yield than with either sole carbon source These results highlight the potential for this multiple carbon source approach to improve the TMCY and balance redox in biosynthetic pathways. Carboxylation is limited to particular metabolic pathways, is not feasible for a wide range of chemicals, incurs high energetic costs, and is often avoided Another method to improve the TMCY is to avoid decarboxylation. The NOG does not generate redox energy and it is not directly applicable for production of high potential energy compounds such as alcohols or esters that depend on redox energy for their synthesis
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