L-arginine biosynthesis via acetylated ornithine

Molecular functions are attached only to leaf annotons. The module-level concept is the biological process, and no module-wide location is asserted because the scope spans bacteria and compartmentalised eukaryotes; the only asserted locations are on the two OTC compartment variants. The module is an abstract cross-taxon reaction template; P. putida KT2440 is one exemplar, and reviewed UniProt accessions from E. coli, B. subtilis, M. tuberculosis, Synechocystis, Nostoc, Methanocaldococcus, S. cerevisiae, S. pombe and Arabidopsis orient the family selectors without making the template species-specific. Two FAMILY_FUNCTION_UNREVIEWED validator warnings are expected and accepted. The PTHR23342 review leaves GO:0004042 UNRESOLVED because animal NAGS shares a subfamily with the NAG kinases, and the PTHR43626 review leaves it UNRESOLVED because the activity is shown only for M. tuberculosis Rv2747. The verified PANTHER ids are kept because they record family membership; the specific activity is carried by the required_function and the reviewed exemplars. The S. cerevisiae ARG5,6 exemplar is labelled by its systematic name, YER069W (yeast ARG5,6), because the comma in the standard name ARG5,6 is not accepted by the symbol-first label convention. PAINT nodes are attached only where a local IBD row names a reviewed molecular-function exemplar; they do not establish species-specific pathway usage. Shared carbamoyl-phosphate production and unrelated arginine catabolism are outside this module. ALIGN with YeastPathways (2026-10; ARGSYNBSUB-PWY and CITRUL-BIO2-PWY, the latter folded in): every YeastCyc reaction maps onto the module. The YeastCyc gene assignments for the arginine enzymes are correct (ARG2, ARG7, ARG5,6, ARG8, ARG3, ARG1, ARG4, CPA1, CPA2); URA2 is listed by YeastCyc for CARBPSYN-RXN but is the pyrimidine CPSase-ATCase and is not adopted. Changes made - a fungal-type NAGS variant (ARG2, arg6; PANTHER PTHR23342:SF4) was added because fungal-type NAGS has a distinct architecture from classical bacterial ArgA; the ArgJ, ArgB, type 1 ArgC, ArgD, ASS and ASL selectors already contain the fungal enzymes, which were added as representatives (ARG5,6 and arg11 under both ArgB and ArgC, as the precursor polyprotein is cleaved into two separate enzymes, so no fused-architecture variant was needed); an optional pathway-dedicated CPS-A part (CPA1/CPA2, arg5/arg4) was added, keeping the original boundary that excludes shared CarAB-type supply; and the OTC step gained a cytosol versus mitochondrial-matrix variant set reflecting ornithine export (S. cerevisiae, ORT1/ARG11) versus citrulline export (S. pombe, with SPBC365.16 assigned in the GO-CAM). The characterized fungal implementation uses ArgJ recycling; an ARG7 deletion is arginine-leaky, so alternative ornithine release must not be excluded (PMID9428669). Mitochondrial carriers (ORT1, SPBC365.16) are transport steps between compartments and are kept outside the enzymatic core. In the characterized yeast systems the ornithine-forming steps (NAGS, ARG5,6, ARG8, ARG7) are mitochondrial-matrix enzymes (PMID:205532). GO-CAM disagreements - YeastPathways_ARGSYNBSUB-PWY places all activities in cytosol, including the mitochondrial ARG2, ARG5,6, ARG8 and ARG7 activities; it types the acetyl-CoA-dependent glutamate acetylation by ARG2 and ARG7 as GO:0103045 (L-methionine N-acyltransferase activity) instead of GO:0004042; and has a single causal edge. The PomBase model (6690711d00000916) agrees with the module's compartment split but omits the arginine-specific CPSase (arg5/arg4) and contains no aga1 acetyl-CoA-dependent activity; that activity is not asserted here without specific support, and also includes arginyl-tRNA ligase (msr1) and arginine import, which are outside this module. Taxon context is an occurrence envelope, not a claim that all species possess or satisfy the complete template. No common compartment is imposed on plant plastids, fungal mitochondria/cytosol and prokaryotes. PII regulation is described on the plant NAGK exemplar but the regulatory partner is outside this biosynthetic reaction core. Arg7 self-processing occurs before mitochondrial targeting (PMID10753950), distinct from Arg5,6 import-dependent processing.

Connections

Optional because many bacteria make carbamoyl phosphate with a single CarA/CarB synthetase shared with pyrimidine biosynthesis, which is kept outside this module. The represented fungal systems have a separate arginine-specific CPS-A (S. cerevisiae CPA1/CPA2, S. pombe arg5/arg4) in addition to the pyrimidine-pathway CPSase-ATCase (S. cerevisiae URA2, S. pombe ura1); only the dedicated enzyme is a module part. YeastPathways also lists URA2 for this reaction, but URA2 is the pyrimidine paralog and is not adopted here.