spoT-dependent accumulation of guanosine tetraphosphate in response to fatty acid starvation in Escherichia coli.

Seyfzadeh, Manouchehr; Keener, John; Nomura, Masayasu

doi:10.1073/pnas.90.23.11004

Cited by 166 publications

(158 citation statements)

References 16 publications

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“…The regulatory loop also works in the other direction. The inhibition of fatty acid synthesis triggers an increase in ppGpp (66), which informs macromolecular biosynthetic systems about the status of membrane biogenesis. The mechanism of ppGpp regulation by fatty acid biosynthesis is not completely clear, but the direct interaction between ACP and ppGpp synthase II (SpoT) (67,68) suggests the acyl-ACP pool may be involved in this process also.…”

Section: Regulatory Roles For the Acyltranferasesmentioning

confidence: 99%

Thematic Review Series: Glycerolipids. Acyltransferases in bacterial glycerophospholipid synthesis

Zhang

Rock

2008

Journal of Lipid Research

118

122

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Phospholipid biosynthesis is a vital facet of bacterial physiology that begins with the synthesis of the fatty acids by a soluble type II fatty acid synthase. The bacterial glycerol-phosphate acyltransferases utilize the completed fatty acid chains to form the first membrane phospholipid and thus play a critical role in the regulation of membrane biogenesis. The first bacterial acyltransferase described was PlsB, a glycerol-phosphate acyltransferase. PlsB is a key regulatory point that coordinates membrane phospholipid formation with cell growth and macromolecular synthesis. Phosphatidic acid is then produced by PlsC, a 1-acylglycerolphosphate acyltransferase. These two acyltransferases use thioesters of either CoA or acyl carrier protein (ACP) as the acyl donors and have homologs that perform the same reactions in higher organisms. However, the most prevalent glycerol-phosphate acyltransferase in the bacterial world is PlsY, which uses a recently discovered acyl-phosphate fatty acid intermediate as an acyl donor. This unique activated fatty acid is formed from the acyl-ACP end products of the fatty acid biosynthetic pathway by PlsX, an acyl-ACP:phosphate transacylase. Bacterial phospholipid synthesis is a vital facet of bacterial physiology, and the phospholipid head group structures found in the bacterial world come in a truly bewildering variety (1). Phosphatidic acid is a universal intermediate in the biosynthesis of these membrane glycerophospholipids in eubacteria, and this review focuses on the two acyltransferase steps that are common reactions in all glycerophospholipid biosynthesis in bacteria, the glycerol-phosphate and 1-acylglycerol-phosphate (LPA) acyltransferases. These enzymes sit at the interface between the soluble type II fatty acid biosynthetic pathway and the creation of a phospholipid molecule that drives membrane expansion. This pivotal position makes the glycerol-phosphate acyltransferases key regulators of both fatty acid and phospholipid synthesis and has spurred considerable research into the function, selectivity, and regulation of the acyltransferase systems. This review will cover the two acyltransferase systems involved in bacterial glycerophospholipid synthesis, the origin and utilization of acyl donors by these pathways, and their roles in regulating membrane biogenesis. ACYL DONORS IN ACYLTRANSFERASE REACTIONSThe most important acyl donor in bacterial glycerolipid synthesis is acyl-acyl carrier protein (ACP). ACP is a 9 kDa protein that is the acyl group carrier in type II fatty acid synthesis and shuttles the intermediates attached to the sulfhydryl group at the terminus of its 4′-phosphopantetheine prosthetic group between the pathway enzymes (2, 3). These acyl donors are the end products of the bacterial dissociated type II fatty acid synthesis pathway, and in most bacteria, type II fatty acid synthesis is the sole source of fatty acids for membrane phospholipid synthesis. An acyl-ACP intermediate has two possible fates. It can reenter the fatty acid elongation cycle...

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Section: Regulatory Roles For the Acyltranferasesmentioning

confidence: 99%

Thematic Review Series: Glycerolipids. Acyltransferases in bacterial glycerophospholipid synthesis

Zhang

Rock

2008

Journal of Lipid Research

118

122

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“…Synthesis of (p)ppGpp by RelA is strongly induced on amino acid limitation by so-called "starved" ribosomal complexes loaded with cognate deacylated tRNA in the A-site (8), and RelA activation is further potentiated by the product of the reaction, ppGpp (9). SpoT has both (p)ppGpp synthesis and hydrolysis activities and is regulated by numerous stress signals, including fatty acid (10), iron (11), and carbon source (6) limitations.…”

mentioning

confidence: 99%

Negative allosteric regulation of Enterococcus faecalis small alarmone synthetase RelQ by single-stranded RNA

Beljantseva

Kudrin

Andresen

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The alarmone nucleotides guanosine pentaphosphate (pppGpp) and tetraphosphate (ppGpp), collectively referred to as (p)ppGpp, are key regulators of bacterial growth, stress adaptation, pathogenicity, and antibiotic tolerance. We show that the tetrameric small alarmone synthetase (SAS) RelQ from the Gram-positive pathogen Enterococcus faecalis is a sequence-specific RNA-binding protein. RelQ's enzymatic and RNA binding activities are subject to intricate allosteric regulation. (p)ppGpp synthesis is potently inhibited by the binding of single-stranded RNA. Conversely, RelQ's enzymatic activity destabilizes the RelQ:RNA complex. pppGpp, an allosteric activator of the enzyme, counteracts the effect of RNA. Tetramerization of RelQ is essential for this regulatory mechanism, because both RNA binding and enzymatic activity are abolished by deletion of the SAS-specific C-terminal helix 5α. The interplay of pppGpp binding, (p)ppGpp synthesis, and RNA binding unites two archetypal regulatory paradigms within a single protein. The mechanism is likely a prevalent but previously unappreciated regulatory switch used by the widely distributed bacterial SAS enzymes. stringent response | (p)ppGpp | RNA-protein interaction | allosteric regulation | nucleotide signaling

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“…SpoT is a bifunctional enzyme with both ppGpp synthetase and hydrolase activities (10,11). Although the regulation of SpoT enzymatic activities is not well understood, SpoT is responsible for ppGpp accumulation in response to carbon, phosphate, fatty acid, and iron starvation conditions (14,21,22). We compared iraP mRNA levels in wt, relA, and relA spoT mutant strains.…”

mentioning

confidence: 99%

ppGpp regulation of RpoS degradation via anti-adaptor protein IraP

Bougdour

Gottesman

2007

Proc. Natl. Acad. Sci. U.S.A.

125

117

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IraP is a small protein that interferes with the delivery of S (RpoS) to the ClpXP protease by blocking the action of RssB, an adaptor protein for S degradation. IraP was previously shown to mediate stabilization of S during phosphate starvation. Here, we show that iraP is transcribed in response to phosphate starvation; this response is mediated by ppGpp. The iraP promoter is positively regulated by ppGpp, dependent on the discriminator region of the iraP promoter. Sensing of phosphate starvation requires SpoT but not RelA. The results demonstrate a target for positive regulation by ppGpp and suggest that the cell use of ppGpp to mediate a variety of starvation responses operates in part by modulating S levels.phosphate starvation ͉ 38 ͉ SpoT B acteria have evolved sophisticated mechanisms to recognize and respond to a variety of environmental stresses. In Escherichia coli, S , the gene product of rpoS, is the factor of the general stress response and adaptation to stationary phase (1, 2). S controls the expression of Ϸ100 genes involved in functions that help cells cope with various kinds of stress. S amounts and activity are tightly regulated (3-5).In exponentially growing cells, the active proteolysis of S is crucial to maintain a low intracellular concentration of this factor (6, 7). S becomes stable as cells are starved or are exposed to certain stresses (reviewed in ref. 4). S protein turnover requires the energy-dependent protease, ClpXP, and the adaptor protein, RssB (SprE), which binds directly to S and targets it to ClpXP (8). RssB has an N-terminal domain of the response regulator family, with a conserved site for phosphorylation. Recently, the identification of an anti-adaptor protein, IraP, provided an explanation for how proteolysis of S can be regulated. In vivo, S is stabilized after phosphate starvation in a manner that depends on IraP and that is independent of RssB phosphorylation. In vitro, IraP inhibits S proteolysis through a direct interaction with RssB (9). Although the inhibitory effect of IraP on S degradation has been observed in response to phosphate starvation, how phosphate starvation is sensed and how this signal affects IraP expression and/or activity has not been described previously. We show in this work that iraP mRNA accumulates in phosphate-starved cells, dependent on the alarmone ppGpp, the global regulator of the stringent response. This induction requires the discriminator sequence of the iraP promoter. Two proteins in E. coli, RelA and SpoT, are capable of synthesizing ppGpp (10, 11); we find that SpoT, but not RelA, is essential for the induction of iraP expression in response to phosphate starvation. The positive regulation of iraP transcription by ppGpp leads to regulation of S proteolysis.Results iraP mRNA Accumulates in Response to Phosphate Starvation. Previous work showed that IraP stabilizes the transcription factor S under phosphate starvation (9). We analyzed by Northern blot the levels of iraP mRNA before and after removal of phosphate. Fig. 1A shows that iraP...

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spoT-dependent accumulation of guanosine tetraphosphate in response to fatty acid starvation in Escherichia coli.

Cited by 166 publications

References 16 publications

Thematic Review Series: Glycerolipids. Acyltransferases in bacterial glycerophospholipid synthesis

Thematic Review Series: Glycerolipids. Acyltransferases in bacterial glycerophospholipid synthesis

Negative allosteric regulation of Enterococcus faecalis small alarmone synthetase RelQ by single-stranded RNA

ppGpp regulation of RpoS degradation via anti-adaptor protein IraP

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