Phospholipids are membrane components. In addition to providing the membrane matrix, phospholipids are also involved in synthesizing several types of surface molecules. The phosphoethanolamine head groups of phosphatidylethanolamine are transferred and attached to the lipopolysaccharide (LPS) core sugars and to periplasmic membrane-derived oligosaccharides (MDO). The head group of phosphatidylglycerol is used for modifying various lipoproteins and MDO. The entire molecule is used in the synthesis of cardiolipin.
The major phospholipids of E. coli are phosphatidylethanolamine (PE), phosphatidylglycerol(PG) and cardiolipin. All phospholipids contain sn-glycerol-3-phosphate esterified with fatty acids at the sn-1 and sn-2 positions.

The genes that code for the enzymes of glycerophospholipid synthesis are scattered around the chromosome. With the exception of phosphatidylglycerophosphate phosphatase (pgp), it appears that there is only a single structural gene coding for each enzyme. While control at the level of transcription may occur, there is no evidence for the clustering of related biosynthetic genes into operons (Ref.1).
========================================================================
PlsY/PlsX pathway is an alternative route to a single enzyme PlsB. Apparently PlsY/PlsX/PlsC pathway and not PlsB/PlsC is the most common route to form one of the most important precursor of all phospholipids in all bacteria.

=====PlsX/PlsY pathway – alternative acyltransferase system (for bacteria lacking plsB):====

This is a two-step pathway that utilizes a new fatty acid intermediate for the initiation of phospholipid formation. First, PlsX produces a unique activated fatty acid by catalyzing the synthesis of fatty acyl-phosphate from acyl-acyl carrier protein, and then PlsY transfers the fatty acid from acyl-phosphate to the 1-position of G3P. The PlsX/Y pathway defines the most widely distributed pathway for the initiation of phospholipid formation in bacteria and represents a new target for the development of antibacterial therapeutics.

From Paoletti L, Lu YJ, Schujman GE, de Mendoza D, Rock CO. “Coupling of fatty acid and phospholipid synthesis in Bacillus subtilis” (2007)(Ref.7):

plsX (acyl-acyl carrier protein [ACP]:phosphate acyltransferase), plsY (yneS) (acyl-phosphate:glycerol-phosphate acyltransferase), and plsC (yhdO) (acyl-ACP:1-acylglycerol-phosphate acyltransferase) function in phosphatidic acid formation, the precursor to membrane phospholipids. The physiological functions of these genes was inferred from their in vitro biochemical activities, and this study investigated their roles in gram-positive phospholipid metabolism through the analysis of conditional knockout strains in the Bacillus subtilis model system. The depletion of PlsX led to the cessation of both fatty acid synthesis and phospholipid synthesis. The inactivation of PlsY also blocked phospholipid synthesis, but fatty acid formation continued due to the appearance of acylphosphate intermediates and fatty acids arising from their hydrolysis. Phospholipid synthesis ceased following PlsC depletion, but fatty acid synthesis continued at a high rate, leading to the accumulation of fatty acids arising from the dephosphorylation of 1-acylglycerol-3-P followed by the deacylation of monoacylglycerol. Analysis of glycerol 3-P acylation in B. subtilis membranes showed that PlsY was an acylphosphate-specific acyltransferase, whereas PlsC used only acyl-ACP as an acyl donor. PlsX was found in the soluble fraction of disrupted cells but was associated with the cell membrane in intact organisms. These data establish that PlsX is a key enzyme that coordinates the production of fatty acids and membrane phospholipids in B. subtilis.

======== plsB===================================================

The sn-glycerol-3-phosphate (G3P) acyltransferase catalyzes the first committed step in membrane phospholipid formation and acylates the 1-position of G3P with either acyl-acyl carrier protein (ACP) or acyl-coenzyme A (CoA) thioesters. The G3P acyltransferase in Escherichia coli has been extensively studied and is the membrane-bound product of the plsB gene. Consistent with its position at the start of the phospholipid biosynthetic pathway, the PlsB protein functions as a sensor that monitors the metabolic state of the cell through its allosteric interactions with ATP and guanosine-3',5'-tetraphosphate to coordinate the rate of G3P acylation with macromolecular biosynthesis and cell growth

======= Cardiolipin===========================================

Cardiolipin is an anionic membrane phospholipid. It is present in the plasma membrane of bacteria, whilst, is a marker lipid of mitochondrial membrane in eukaryotes. Along with phosphatidylglycerol, the anionic lipids are important for the biogenesis and function of the mitochondrial membrane.

The difference of cardiolipin biosynthesis between bacteria and eukaryotes lies in the last step. Whereas in bacteria, two molecules of phosphatidylglycerol are condensed to form cardiolipin, in eukaryotes, cardiolipin is formed from one molecule of CDP-diacylglycerol and one molecule of phosphatidylglycerol. In all eukaryotes, cardiolipin biosynthesis occurs in the inner mitochondrial membrane

======= Phosphatidic acid==========================================

Phosphatidic acid (PtdOH) is an essential substrate for enzymes involved in the synthesis of glycerophospholipids and triacylglycerols. PtdOH enters the biosynthetic pathway of phospholipids through a CTP-dependent activation catalyzed by CDP-diacylglycerol synthase. This enzyme forms CDP-diacylglycerol, which serves as a direct precursor for phosphatidylinositol (PtdIns), phosphatidylglycerol (PtdGro) and cardiolipin (di-PtdGro). In yeast, phosphatidylserine (PtdSer) is also formed from CDP-diacylglycerol, whereas PtdSer of mammalian cells is synthesized by head-group exchange of phosphatidylethanolamine (PtdEtn) or phosphatidylcholine (PtdCho). PtdSer can be decarboxylated to PtdEtn which is finally converted to PtdCho by three methylation steps

Phosphatidic acid (PtdOH) is a key intermediate in glycerolipid biosynthesis. Two different pathways are known for de novo formation of this compound, namely (a) the Gro3P (glycerol 3-phosphate) pathway, and (b) the GrnP (dihydroxyacetone phosphate) pathway. Whereas the former route of PtdOH synthesis is present in bacteria and all types of eukaryotes, the GrnP pathway is restricted to yeast and mammalian cells.

The plsB gene of E. coli encodes a 83-kDa. The enzymatic activity of Gro3P AT was found to be firmly associated with the inner membrane of E. coli with the active site facing the cytosol. Only a small part of this protein, if any, traverses the membrane bilayer.
The enzyme catalyzing the second acylation step during PtdOH formation in E. coli, 1-acyl-Gro3P AT, is encoded by the plsC gene. In contrast to Gro3P AT, 1-acyl-Gro3P AT has a molecular mass of only 25 kDa, although both enzymes catalyze essentially the same type of reaction. Because the Gro3P AT reaction is the rate limiting step in Phosphatidic acid biosynthesis, it has been speculated that the larger size of the enzyme may allow the binding of effectors necessary for balanced PtdOH production.

================NOTES:==========================================

It is possible that gpsA, glpA, and glpD are able to perform the same function, therefore presence of one of the above enzymes complete the pathway.
Note: cdh, according to the KEGG map reversed the formation of CDP-diacylglycerol. Absence of that enzyme does not influence the formation major glycerophospholipids such as: Cardiolipin, phosphatidyl-glycerophosphate; phosphatidyl-l-Serine, and phosphatidyl-ethanolamine.

ALDEHYDE DEHYDROGENASE(EC 1.2.1.3)

- Is very similar to Aldehyde Dehydrogenase B (EC 1.2.1.22) in Salmonella and certain
species of Escherichia and Yersinia.
- homologous to glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.9) in Streptomyces,
streptococcus, clostridium
--> This may mean that within these organisms, aldehyde dehydrogenase is playing
two functional roles.
- does not appear in Borrelia, Cambylobacter, Thermatoga, Desulfovibrio (no homlogues
found)

======Abbreviations for Glicerophospholipid pathway products:=========

Cardiolipin - Cdl
Phosphatidyl-Glycerophosphate - PGP
Phosphatidyl-l-Serine - PS
Phosphatidyl-Ethanolamine - PE
Phosphatidyl-Glycerol - PG

==========REFERENCES:==================================

1. Athenstaedt K, Daum G. Phosphatidic acid, a key intermediate in lipid metabolism.
Eur J Biochem. 1999 Nov;266(1):1-16. Review. PMID: 10542045;

2. Raetz CR, Dowhan W (1990). Biosynthesis and function of phospholipids in Escherichia coli. J Biol Chem 1990;265(3);1235-8. PMID: 2404013

3.Spoering, A. L., Vulic, M., Lewis, K. (2006). GlpD and PlsB Participate in Persister Cell Formation in Escherichia coli. J. Bacteriol. 188: 5136-5144

4.Gonzalez-Baro, M. R., Granger, D. A., Coleman, R. A. (2001). Mitochondrial Glycerol Phosphate Acyltransferase Contains Two Transmembrane Domains with the Active Site in the N-terminal Domain Facing the Cytosol. J. Biol. Chem. 276: 43182-43188.

5.Zheng, Z., Zou, J. (2001). The Initial Step of the Glycerolipid Pathway. IDENTIFICATION OF GLYCEROL 3-PHOSPHATE/DIHYDROXYACETONE PHOSPHATE DUAL SUBSTRATE ACYLTRANSFERASES IN SACCHAROMYCES CEREVISIAE. J. Biol. Chem. 276: 41710-41716.

6. Lu YJ, Zhang YM, Grimes KD, Qi J, Lee RE, Rock CO. Acyl-phosphates initiate membrane phospholipid synthesis in Gram-positive pathogens.Mol Cell. 2006 Sep 1;23(5):765-72.PMID: 16949372

7. Paoletti L, Lu YJ, Schujman GE, de Mendoza D, Rock CO.Coupling of fatty acid and phospholipid synthesis in Bacillus subtilis.J Bacteriol. 2007 Aug;189(16):5816-24. Epub 2007 Jun 8.PMID: 17557823

8. Yoshimura M, Oshima T, Ogasawara N. Involvement of the YneS/YgiH and PlsX proteins in phospholipid biosynthesis in both Bacillus subtilis and Escherichia coli. BMC Microbiol. 2007 Jul 24;7:69.PMID: 17645809.

9. Zhang YM, Rock CO. Thematic review series: Glycerolipids. Acyltransferases in bacterial glycerophospholipid synthesis. J Lipid Res. 2008 Sep;49(9):1867-74. Review. PMID: 18369234.

10. H. Shindou and T. Shimizu. Acyl-CoA:Lysophospholipid Acyltransferases J. Biol. Chem., January 2, 2009; 284(1): 1 - 5. PMID: 18718904