Fermentative Pyruvate and Acetyl-Coenzyme A Metabolism
Ecosal Plus
|October 8, 2015
Summary
Pyruvate formate lyase (PFL) is key in enterobacteria fermentation, converting pyruvate to acetyl-CoA and formate. Its regulation impacts central metabolism, influencing pathways like acetate and ethanol production, and D-lactate formation in mutants.
Area of Science:
- Microbiology
- Biochemistry
- Metabolic Engineering
Background:
- Central metabolism relies on pyruvate and acetyl-CoA.
- Mixed-acid fermentation in enterobacteria features pyruvate formate lyase (PFL) activity.
- Formic acid from pyruvate cleavage contributes significantly to carbon flux.
Purpose of the Study:
- To elucidate the regulatory mechanisms of pyruvate metabolism in enterobacteria.
- To understand the role of PFL and its activase in central carbon flow.
- To differentiate fermentation pathways leading to acetate, ethanol, or 2,3-butanediol.
Main Methods:
- Enzyme kinetics studies of pyruvate formate lyase and related enzymes.
- Analysis of metabolic flux in wild-type and mutant enterobacteria strains.
- Investigating the control of PFL activation by PFL-activase.
- Assessing the impact of NADH:NAD+ ratio on fermentation product formation.
Main Results:
- PFL catalyzes pyruvate to acetyl-CoA and formate, a key step in mixed-acid fermentation.
- Acetyl-CoA metabolism branches into acetate or ethanol production, regulated by cellular energy demands (ATP) and redox balance (NADH).
- Mutants lacking acetate or ethanol pathways redirect pyruvate to D-lactate via D-lactate dehydrogenase when PFL is inactive.
- Some enterobacteria (e.g., Klebsiella) produce 2,3-butanediol via α-acetolactate synthase (ALS) and subsequent reactions, differing from the typical mixed-acid pathway.
Conclusions:
- The PFL-catalyzed reaction is central to enterobacterial fermentation, with its activity and downstream acetyl-CoA metabolism tightly regulated.
- Cellular redox state (NADH:NAD+ ratio) and energy requirements dictate the metabolic fate of pyruvate and acetyl-CoA.
- Alternative fermentation pathways, such as 2,3-butanediol production, exist in certain enterobacterial genera, highlighting metabolic diversity.
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