Thematic Review Series: Glycerolipids. Acyltransferases in bacterial glycerophospholipid synthesis

Abstract

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...

Acyltransferases in Bacteria

“…7). Different types and common features of bacterial glycerolipid acyltransferases have already been excellently reviewed by Zhang and Rock (66); therefore, this review will present only central aspects necessary to provide a general overview of this important family of acyltransferases in bacteria.…”

“…In general, these enzymes share the ability to transfer thioester-activated acyl substrates to a hydroxyl or amine acceptor to form an ester or amide bond, such as acyltransferases that synthesize glycerolipids, nonribosomal peptide synthetases, acyltransferases in-volved in lipid A biosynthesis, polyketide-associated acyltransferases, or chloramphenicol acetyltransferase (CAT). The catalytically active histidine in this motif initiates the deprotonation of a hydroxyl group to enable the nucleophilic attack on the acyl donor (61)(62)(63)(64)(65)(66)(67).…”

Superessential reactions in metabolic networks

“…The enzyme uses fatty acyl-ACP or acyl-CoA thioesters to form acylglycerol-3-phosphate, and it is mainly limited to γ-proteobacteria (38), which explains its low genome occurrence index. Other prokaryotes contain a similar enzyme that uses acyl-phosphate to synthesize acyl-glycerol-3-phosphate (encoded by the gene plsY), but the Kegg reaction database does not distinguish between these reactions.…”

Massive Formation of Intracellular Membrane Vesicles in Escherichia coli by a Monotopic Membrane-bound Lipid Glycosyltransferase

“…Interestingly, PlsB (cf. above) is considered to function as a sensor for coordination of membrane protein synthesis and phospholipid formation in E. coli (74). It has been established recently that plus-charged proteins and peptides can bind and thereby withdraw the minus-charged phospholipids PG and CL from the free pool in a bilayer (59,75).…”