Prokaryotic molybdenum cofactor biosynthesis from GTP to Mo-molybdopterin and optional dinucleotide variants

A reusable prokaryotic module for molybdenum cofactor biosynthesis constructs the pyranopterin dithiolene ligand from GTP, loads it with molybdenum, and may append a nucleotide to produce a client-class-specific cofactor variant. MoaA first performs radical-SAM cyclization of GTP and MoaC rearranges the cyclic intermediate to cyclic pyranopterin monophosphate (cPMP). Molybdopterin synthase then inserts two sulfurs: MoeB activates the small MoaD sulfur carrier, and the MoaD-MoaE synthase converts cPMP to molybdopterin (MPT). Across prokaryotic realizations, MPT is adenylylated by a separate bacterial MogA or by a catalytically competent prokaryotic MoaB lineage, and MoeA then inserts molybdate to form Mo-MPT. Some realizations stop at Mo-MPT, whereas others use MobA to make MGD or MocA to make MCD. The module excludes upstream sulfur supply, molybdate transport, terminal cofactor sulfuration, cofactor insertion into client apoenzymes, mature molybdoenzyme reactions, pathway regulation, eukaryotic MOCS/CNX/GPHN fusion organization, and human disease.

Scope and generalization: the MoaA-MoaC-MoaD/MoaE-MoeB-MogA/MoaB-MoeA chemistry, with the MobA and MocA dinucleotide branches, is conserved across bacteria and archaea, so the module is prokaryote-wide. Pseudomonas putida KT2440 is one exemplar and Escherichia coli K-12 is the biochemically characterized reference. Pyrococcus furiosus anchors the catalytically active MoaB alternative. Eukaryotic MOCS1/MOCS2/MOCS3/gephyrin organization is excluded, although several PANTHER families used here also contain those proteins. The scope stays CONCRETE because every leaf grounds to experimentally characterized representatives. Family groundings follow the PANTHER/PTN groundings proposed in PR #5076 where the family reviews verified them: MoeB SF194 with PTN000102040, MogA SF1 with PTN000022863, MoeA PTHR10192 with PTN000022760, and MobA SF81 with PTN001452257. Two were narrowed. MoaA keeps PTN000539172 but asserts no PTHR22960 family id, because that parent family also holds the MoaC cPMP synthases. MoaE is grounded on PTHR23404:SF2 instead of the parent, because the parent also holds the MBIP subfamily. The Listeria welshimeri MoaC exemplar (A0AHF9), which has no experimental evidence, was dropped. E. coli MoaC (P0A738) is not an SF29 representative because PANTHER assigns it no subfamily. P. putida KT2440 has no separate mogA gene; its two MoaB-family paralogs, moaB-I (Q88L15) and moaB-II (Q88E67), are not grounded here because neither has been shown to adenylate MPT (see the MoaB knowledge gap). KT2440 is therefore an exemplar for every step except MPT adenylylation. A KT2440 realization leaves that step as a REALIZER gap (the activity is required but its carrier is unidentified), not as evidence that the step is absent. The P. furiosus MoaB anchor comes from a tungsten-cofactor organism; it is used here for the adenylyl transfer, which PMID:18154309 reports is shared by W and Mo cofactor maturation. Its gene review therefore uses the parent process GO:0032324, while this module's process concept is the Mo-specific GO:0006777.