Guanosine tetraphosphate inhibition of fatty acid and phospholipid synthesis in Escherichia coli is relieved by overexpression of glycerol-3-phosphate acyltransferase (plsB)

Heath, R J; Jackowski, S; Rock, C O

doi:10.1016/s0021-9258(18)47234-1

Cited by 123Lipid metabolism and biosynthesisBacterial Genetics and BiotechnologyMicrobial Metabolic Engineering and Bioproduction

Guanosine tetraphosphate inhibition of fatty acid and phospholipid synthesis in Escherichia coli is relieved by overexpression of glycerol-3-phosphate acyltransferase (plsB)

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Heath, R J, Jackowski, S, Rock, C O·1994·Journal of Biological Chemistry

DOI 10.1016/s0021-9258(18)47234-1

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Abstract

The accumulation of the alarmone guanosine-3',5'-bispyrophosphate (ppGpp) in response to amino acid starvation or energy source depletion mediates the coordinate inhibition of macromolecular and membrane phospholipid biosynthesis in Escherichia coli. Accumulation of ppGpp triggered by the induced expression of either the relA gene or an unregulated, truncated relA gene that encodes a constitutively active ppGpp synthetase I, inhibited both de novo fatty acid and phospholipid biosynthesis and the incorporation of exogenous fatty acids into phospholipid. ppGpp inhibition of fatty acid and phospholipid synthesis was associated with an accumulation of long-chain acyl-ACP, the end products of fatty acid biosynthesis, and substrates for the sn-glycerol-3-phosphate acyltransferase (the plsB gene product). Overexpression of the plsB gene product relieved the inhibition of fatty acid and phospholipid synthesis, prevented the accumulation of long-chain acyl-ACPs, and allowed an increase in cell size following elevation of intracellular ppGpp. However, stable RNA accumulation and cell division were still blocked by ppGpp accumulation. These data show that the sn-glycerol-3-phosphate acyltransferase mediates the ppGpp-dependent regulation of fatty acid and phospholipid biosynthesis in E. coli.

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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 Heath et al. 1994

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Authors: Heath, R. J., Jackowski, S., & Rock, C. O.
Affiliations: St. Jude Children's Research Hospital (US)
ORCID: Heath, R J
Jackowski, S
Rock, C O
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1994-10
Volume: 269
Issue: 42
Pages: 26584-26590
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1016/s0021-9258(18)47234-1
OpenAlex: W1573477696
Cited by: 123
References: 49
Citations by year: 2026: 3 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 1 · 2020: 7 · 2019: 5 · 2018: 9 · 2017: 5 · 2016: 7 · 2015: 4 · 2014: 6 · 2013: 6 · 2012: 7
FWCI: 3.13
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 9507 d)
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 › Genetics › Bacterial Genetics and Biotechnology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
Keywords: ppGpp, alarmone, fatty acid synthesis, phospholipid synthesis, glycerol-3-phosphate acyltransferase, RelA, cell size, cell division, RNA accumulation, Escherichia coli, amino acid starvation, energy depletion
MeSH terms: Acetates, Acyl Carrier Protein, Escherichia coli, Fatty Acids, Glycerol-3-Phosphate O-Acyltransferase, Guanosine Tetraphosphate, Phospholipids, Acetic Acid

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Guanosine tetraphosphate inhibition of fatty acid and phospholipid synthesis in Escherichia coli is relieved by overexpression of glycerol-3-phosphate acyltransferase (plsB)

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