Researchers have identified a missing metabolic pathway that has turned out to be the most widely distributed acyltransferase system in bacteria, according to a recent report in Molecular Cell.

Phosphatidic acid is a key intermediate in the synthesis of membrane phospholipids. In the model Gram-negative organism Escherichia coli , the first step in the formation of phosphatidic acid is the acylation of glycerol-3-phosphate (G3P). This step is carried out by PlsB, a G3P acyltransferase that uses either acyl-ACP (ACP is an acyl-acyl carrier protein) or acyl-coenzyme A to add an acyl group to G3P. However, Gram-positive bacteria do not produce PlsB and in some Gram-negative organisms, plsB is non-essential, indicating that there must be another pathway capable of carrying out this key reaction.

Ying-Jie Lu and colleagues began investigating phosphatidic acid synthesis in the Gram-positive organism Streptococcus pneumoniae . Previous work in E. coli had identified another protein, PlsX, which it was thought might be involved in G3P metabolism. Biochemical analysis of the activity of S. pneumoniae PlsX showed that it had no intrinsic G3P-acyltransferase or fatty-acid kinase activity. Rather, it was found that S. pneumoniae PlsX is a soluble phosphotransacylase that catalyses the reversible conversion of the end product of type II fatty-acid biosynthesis, acyl-ACP, to a fatty-acyl phosphate, a new metabolic intermediate.

The authors then wondered whether there could be a second protein that used this activated fatty-acid intermediate to generate acylated G3P. They analysed the acyl-phosphate-dependent G3P-acylation activity in S. pneumoniae and found that, in contrast to E. coli, the main S. pneumoniae G3P acyltransferase activity requires an acyl-phosphate as the acyl donor. The protein responsible for this activity in S. pneumoniae was identified as the membrane-associated protein PlsY.

Analysis of the distribution of plsX and plsY revealed that the PlsX/Y pathway is widespread, with plsX and plsY present in 314 of the 395 complete and draft sequences examined. By contrast, plsB was only found in 102 of the 395 genomes examined, and was mainly confined to the γ-proteobacteria. So, it seems that Lu et al. have identified the main pathway responsible for the first step of phosphatidic acid biosynthesis in bacteria.