Bacterial glutamate-to-P5C branch of proline biosynthesis

Bacterial split-enzyme conversion of L-glutamate to L-glutamate 5-semialdehyde: a ProB-family kinase, including the Bacillus ProJ paralog, phosphorylates glutamate with ATP, and ProA reduces L-glutamyl 5-phosphate with NADPH. Spontaneous cyclization yields pyrroline-5-carboxylate (P5C). The module ends before ProC-type P5C reduction to proline and does not require a ProB–ProA complex.

The Bacteria scope describes the split-enzyme route where present, not universal possession or exclusivity. The nine member proteins represent Pseudomonadota, Bacillota and Actinomycetota. Fungi and some archaea also use split enzymes, but lie outside this bacterial module; fused plant/animal P5CS is a different architecture. In Bacillus, ProB and ProJ are alternative kinases feeding a shared ProA. Their anabolic versus osmoadaptive regulation does not define different chemical steps. The 2011 Bacillus genetics used JH642 derivatives rather than the strain-168 reference proteins; the 1996 Corynebacterium study used ATCC17965 rather than the ATCC13032 reference proteins. Curated HAMAP assignments support those reference proteins, and the strain differences remain explicit in their reviews. ProJ feedback resistance is a physiological hypothesis in the 2011 paper, not a measured inhibition constant. Residual growth and asd complementation of a Corynebacterium proA mutant indicate a possible bypass, so absence of a canonical family is not proof that a cell cannot form P5C. PMID:39514317 challenges obligatory ProB–ProA substrate channeling in E. coli; a transient complex is not required by this module, and neither a negative pulldown alone nor that E. coli study is treated as a universal absence result. The kinase PANTHER family includes divergent isopentenyl phosphate kinases in SF1, while SF3 includes bacteria, archaea, fungi and protists. PTHR11063 includes monofunctional ProA and fused P5CS. Thus family membership must be combined with the specified activity and split-polypeptide architecture. No new PAINT placement is inferred from the donor list or from GOA nodes missing in the committed tree slice. RNA binding shown for E. coli ProB in 2023 is not a required pathway activity and is not transferred to all PUA-containing family members. The PSEPK KEGG carbapenem-bucket label is historical partition provenance, not evidence for carbapenem synthesis by this pair.