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A citric acid cycle-deficient Escherichia coli as an efficient chassis for aerobic fermentations
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A citric acid cycle-deficient Escherichia coli as an efficient chassis for aerobic fermentations
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A citric acid cycle-deficient Escherichia coli as an efficient chassis for aerobic fermentations
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Journal Article
A citric acid cycle-deficient Escherichia coli as an efficient chassis for aerobic fermentations
2024
Overview
Tricarboxylic acid cycle (TCA cycle) plays an important role for aerobic growth of heterotrophic bacteria. Theoretically, eliminating TCA cycle would decrease carbon dissipation and facilitate chemicals biosynthesis. Here, we construct an
E. coli
strain without a functional TCA cycle that can serve as a versatile chassis for chemicals biosynthesis. We first use adaptive laboratory evolution to recover aerobic growth in minimal medium of TCA cycle-deficient
E. coli
. Inactivation of succinate dehydrogenase is a key event in the evolutionary trajectory. Supply of succinyl-CoA is identified as the growth limiting factor. By replacing endogenous succinyl-CoA dependent enzymes, we obtain an optimized TCA cycle-deficient
E. coli
strain. As a proof of concept, the strain is engineered for high-yield production of four separate products. This work enhances our understanding of the role of the TCA cycle in
E. coli
metabolism and demonstrates the advantages of using TCA cycle-deficient
E. coli
strain for biotechnological applications.
While tricarboxylic acid cycle (TCA cycle) is required for heterotrophic microbes, it reduces carbon yield of industrial products due to the release of excess CO2. Here, the authors construct an
E. coli
strain without a functional TCA cycle and demonstrate its feasibility as a chassis strain for production of four separate compounds.
