Cited by 88Lipid metabolism and biosynthesisCancer, Lipids, and MetabolismMicrobial Metabolic Engineering and Bioproduction

Regulation of Malonyl-CoA Metabolism by Acyl-Acyl Carrier Protein and β-Ketoacyl-Acyl Carrier Protein Synthases in Escherichia coli

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Heath, Richard J., Rock, Charles O.·1995·Journal of Biological Chemistry

Abstract

The cessation of phospholipid biosynthesis by the inhibition of the sn-glycerol-3-phosphate acyltransferase using a plsB mutant led to an accumulation of long chain acyl-acyl carrier proteins (acyl-ACP) and the concomitant inhibition of de novo fatty acid biosynthesis in Escherichia coli. Malonyl-CoA did not accumulate when phospholipid and fatty acid synthesis was blocked. However, the inactivation of beta-ketoacyl-ACP synthases I and II with the antibiotic cerulenin triggered a large increase in the accumulation of malonyl-CoA following the cessation of phospholipid synthesis, illustrating that the beta-ketoacyl-ACP synthases were responsible for the degradation of malonyl-CoA in the presence of long chain acyl-ACP. The acyl-ACP requirement for malonyl-CoA degradation activity was confirmed by shifting enoyl-ACP reductase mutants (fabI(Ts)) to the non-permissive temperature, leading to the abrupt cessation of fatty acid synthesis and the accumulation of malonyl-CoA in the absence of cerulenin. Analysis of the ACP pool composition before and after the temperature shift showed that the fabI block did not result in the accumulation of long chain acyl-ACP. These data indicate a feedback regulatory loop that functions to recycle malonyl-CoA to acetyl-CoA following the down-regulation of fatty acid and phospholipid formation and provides a physiological rationale for the acyl-ACP-dependent, malonyl-ACP decarboxylase reaction catalyzed by beta-ketoacyl-ACP synthases I and II.

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Crossref · 10.1074/jbc.270.26.15531

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Authors
Heath, R. J., & Rock, C. O.
Affiliations
St. Jude Children's Research Hospital (US)
Corresponding author
Rock, Charles O.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1995-06
Volume
270
Issue
26
Pages
15531-15538
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1967644082
Cited by
88
References
36
Citations by year
2026: 4 · 2025: 1 · 2024: 5 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 2 · 2016: 6 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 3
FWCI
3.25
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute (CA21765, P30CA021765)
  • National Institute of General Medical Sciences (GM 34496)
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
acyl-acyl carrier protein, beta-ketoacyl-ACP synthase, fatty acid synthesis, phospholipid synthesis, feedback regulation, cerulenin, enoyl-ACP reductase, FabI, Escherichia coli
MeSH terms
Acetyl Coenzyme A, Acyl Carrier Protein, Escherichia coli, Fatty Acids, Malonyl Coenzyme A, Phospholipids, 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase

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