Overproduction of Acetyl-CoA Carboxylase Activity Increases the Rate of Fatty Acid Biosynthesis in Escherichia coli
Open accessAbstract
Acetyl-CoA carboxylase (ACC) catalyzes the first committed step of the fatty acid synthetic pathway. Although ACC has often been proposed to be a major rate-controlling enzyme of this pathway, no direct tests of this proposal in vivo have been reported. We have tested this proposal in Escherichia coli. The genes encoding the four subunits of E. coli ACC were cloned in a single plasmid under the control of a bacteriophage T7 promoter. Upon induction of gene expression, the four ACC subunits were overproduced in equimolar amounts. Overproduction of the proteins resulted in greatly increased ACC activity with a concomitant increase in the intracellular level of malonyl-CoA. The effects of ACC overexpression on the rate of fatty acid synthesis were examined in the presence of a thioesterase, which provided a metabolic sink for fatty acid overproduction. Under these conditions ACC overproduction resulted in a 6-fold increase in the rate of fatty acid synthesis.
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An increase in the activity levels of GPAT, PlsX and a fatty acyl-ACP thioesterase (tesA) overcomes this inhibition by detaching the fatty acid from the lipid biosynthesis.
“It appears that an increase in the activity levels of GPAT, PlsX and a fatty acyl-ACP thioesterase (tesA, EC 3.1.2.14) overcomes this inhibition by detaching the fatty acid from the lipid biosynthesis (Davis et al. 2000; Heath et al. 1994; Paoletti et al. 2007).”
From Renewable energy from Cyanobacteria: energy production optimization by metabolic pathway engineering (2011) · cites this paper as Davis et al. 2000
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- Authors
- Davis, M. S., Solbiati, J., & Cronan, J. E.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Cronan, John E.
- ORCID
- Cronan, John E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-09
- Volume
- 275
- Issue
- 37
- Pages
- 28593-28598
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1993899465
- Cited by
- 479
- References
- 41
- Citations by year
- 2026: 11 · 2025: 22 · 2024: 24 · 2023: 15 · 2022: 20 · 2021: 22 · 2020: 26 · 2019: 27 · 2018: 32 · 2017: 35 · 2016: 34 · 2015: 27 · 2014: 38 · 2013: 34 · 2012: 21
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Keywords
- acetyl-CoA carboxylase, fatty acid synthesis, Escherichia coli, enzyme overexpression, malonyl-CoA, thioesterase
- MeSH terms
- Acetyl-CoA Carboxylase, Escherichia coli, Fatty Acids
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