Bacterial phosphatidylglycerol and cardiolipin biosynthesis

A reusable bacterial membrane-lipid module from CDP-diacylglycerol to phosphatidylglycerol and on to phospholipase-D-family cardiolipin. PgsA forms phosphatidylglycerol phosphate, PgpA-type phosphatases remove its terminal phosphate to give phosphatidylglycerol, and one or more Cls lineages form cardiolipin. ClsA and ClsB transfer a phosphatidyl group between two phosphatidylglycerol molecules; ClsC transfers it from phosphatidylethanolamine to phosphatidylglycerol. The route is conserved across Proteobacteria and is exemplified here by Escherichia coli K-12, where every step is characterized experimentally, and by Pseudomonas putida KT2440.

The root is one connected route with two nested parts rather than two unrelated modules. The phosphatidylglycerol part is independently useful and can terminate at phosphatidylglycerol, a bulk membrane lipid and the substrate for other pathways. The cardiolipin part describes the downstream branch; it does not imply that all phosphatidylglycerol is committed to cardiolipin. CDP-diacylglycerol synthesis, the phosphatidylethanolamine and phosphatidylcholine branches, phosphatidylglycerol modification, cardiolipin turnover and acyl-chain remodeling are outside the boundary. Scope and generalization: the module is species-neutral. E. coli K-12 is the experimental exemplar for every step and P. putida KT2440 a second, homology-based exemplar. The PG-dependent PLD-type cardiolipin synthase also occurs in Firmicutes (B. subtilis ClsA, PTHR21248:SF22), but no Firmicute is used as a representative because those genes are not yet reviewed here. The eukaryotic CDP-diacylglycerol-dependent cardiolipin synthase (PTHR14269:SF60) belongs to the separate cdp_dag_phospholipid_synthesis module. Grounding: each step uses the PANTHER subfamily that holds its exemplars, checked against the family reviews. PgsA is PTHR14269:SF62, whose PGP synthase activity is scoped to SF62/SF40 with the Streptomyces clsA member excepted. PgpA is PTHR36305:SF1, scoped to the PGP phosphatases with the Bacteroides inositol-lipid phosphatase BT_1525 excepted. ClsA, ClsB and ClsC are PTHR21248 SF22, SF23 and SF12. The PANTHER SF22 name (PHOSPHOLIPASE D) is the official label; its members are ClsA-type cardiolipin synthases. The route itself is bacteria-wide, but the PgpA grounding is proteobacterial: the PTHR36305 review restricts the PGP phosphatase activity to the Pseudomonadota PAINT node, so the PgpA node carries its own Pseudomonadota context, and other bacteria may use unrelated PGP phosphatases. PgpA is one of three unrelated E. coli PGP phosphatases; PgpB (PAP2 family) and PgpC are not modeled as separate variants. E. coli ClsB can also make phosphatidylglycerol from phosphatidylethanolamine and glycerol, a PgsA-independent side route that is not modeled. The ClsC annoton is grounded to the ClsC subfamily (SF12) with E. coli ClsC as its only representative. The PTHR21248 review leaves GO:0090483 UNRESOLVED for SF12 as a whole because the other members are uncharacterized, so any family-function coverage warning for this annoton reflects that truthful gap. P. putida PP_5276 (SF12) is a candidate third KT2440 synthase, recorded under knowledge gaps.