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.

MODULE:molybdenum_cofactor_biosynthesisDRAFTCONCRETEMetabolic Pathwaymodules/molybdenum_cofactor_biosynthesis.yaml
Mo-molybdopterin cofactor biosynthetic processGO:0006777
file:modules/molybdenum_cofactor_biosynthesis-deep-research-openscientist.md
OpenScientist research for the reusable molybdenum-cofactor biosynthesis module
The report was critically restricted to conserved cofactor-building chemistry; organism-specific disease, transport, sulfuration, and client-enzyme material is outside the module boundary.
15Nodes
10Parts
2Variant Sets
4Variants
10Annotons
6Connections

Derived QC

Recommended-field compliance

76.0% recommended fields populated
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Module deep research

✓ present

  • molybdenum_cofactor_biosynthesis-deep-research-openscientist.md (openscientist)

Leaf nodes lacking representative members

3 leaf node(s) with no concrete protein grounding:

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (9/16 grounded genes reviewed)

9 complete review(s) · 9 with deep research · 7 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
Listeria welshimeri MoaC exemplar A0AHF9 ✗ — —
moaA Q88E69 ✓ ✓ ✓
moaC Q88NC0 ✓ ✓ ✓
moaD Q88NB9 ✓ ✓ ✓
moaE Q88NB8 ✓ ✓ ✓
mobA Q88HA3 ✓ ✓ ✓
moeA Q88L14 ✓ ✓ ✓
moeB Q88PW3 ✓ ✓ ✓
Escherichia coli MogA exemplar P0AF03 ✗ — —
Escherichia coli MoeB exemplar P12282 ✗ — —
Escherichia coli MoaD exemplar P30748 ✗ — —
Escherichia coli MobA exemplar P32173 ✗ — —
PP_2483 Q88K10 ✓ ✓ ✓
PP_4230 Q88F68 ✓ ✓ ✓
Escherichia coli MocA exemplar Q46810 ✗ — —
Pyrococcus furiosus MoaB Q8U3T3 ✗ — —

Details

Prokaryotic molybdenum cofactor biosynthesisMetabolic Pathwaymolybdenum_cofactor_biosynthesis

Conserved prokaryotic formation of Mo-MPT from GTP with optional MGD and MCD nucleotide maturation.

Mo-molybdopterin cofactor biosynthetic processGO:0006777

Connections

cpmp_formation -> mpt_formation Provides Input For
cPMP is the pterin substrate for sulfur insertion by molybdopterin synthase.
mpt_formation -> mo_mpt_formation Provides Input For
MPT is activated and loaded with molybdate to form Mo-MPT.
Mo-MPT may be retained directly or converted to MGD and/or MCD.
Part 1: cyclic pyranopterin monophosphate formation
Cyclic pyranopterin monophosphate formationMetabolic Pathwaycpmp_formation

Two sequential reactions convert GTP to cPMP.

Connections

The cyclic GTP product of MoaA is the substrate for MoaC.
Part 1: radical-SAM GTP cyclization
MoaA GTP cyclizationReactionmoaA_gtp_cyclization

Annotons

MoaA GTP 3',8'-cyclase
moaA_gtp_38_cyclase
Participant: Ortholog Of: PSEPK canonical MoaA
Ortholog Of:
PSEPK canonical MoaAUniProtKB:Q88E69 Orthologs of the curated KT2440 moaA/PP_4597 enzyme that retain canonical GTP 3',8'-cyclase specialization; broader MoaA-like radical-SAM paralogs require gene-specific adjudication.

Function

GTP 3',8'-cyclase activityGO:0061798
Substrates: GTP S-adenosyl-L-methionine
Products: (8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate
Cofactors: two [4Fe-4S] clusters

Forms the cyclic GTP intermediate used by MoaC.

file:interpro/panther/PTHR22960/PTHR22960-entries.csv
The local PANTHER export contains PSEPK Q88E69 and E. coli P30745 as MoaA-lineage proteins.
file:PSEPK/moaA/moaA-ai-review.yaml
The curated KT2440 review accepts GO:0061798 for Q88E69 and distinguishes it from divergent MoaA-family paralogs.
Part 2: cyclic intermediate rearrangement to cPMP
MoaC cPMP synthesisReactionmoaC_cpmp_synthesis

Annotons

MoaC cyclic pyranopterin monophosphate synthase
moaC_cpmp_synthase
Participant: Family: bacterial MoaC cPMP synthase family
Family:
bacterial MoaC cPMP synthase familyPANTHER:PTHR22960:SF29
Representative Members: PSEPK moaC exemplarUniProtKB:Q88NC0 Listeria welshimeri MoaC exemplarUniProtKB:A0AHF9

Function

cyclic pyranopterin monophosphate synthase activityGO:0061799
Substrates: (8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate
Products: cyclic pyranopterin monophosphate (cPMP) diphosphate

Rearranges the MoaA product to cPMP.

file:interpro/panther/PTHR22960/PTHR22960-entries.csv
The local PANTHER export contains Q88NC0 and A0AHF9 in cPMP synthase subfamily PTHR22960:SF29.
file:PSEPK/moaC/moaC-ai-review.yaml
The curated KT2440 review accepts cyclic pyranopterin monophosphate synthase activity for Q88NC0.
Part 2: sulfur-carrier activation and molybdopterin synthesis
Sulfur-carrier activation and MPT formationMetabolic Pathwaympt_formation

MoeB activates MoaD; sulfur-loaded MoaD and MoaE then convert cPMP to MPT.

Connections

Activated MoaD is sulfur-loaded by an external sulfur-donor system before supplying the MoaE reaction.
Part 1: MoaD sulfur-carrier activation
MoeB-dependent MoaD activationReactionmoaD_activation

Annotons

MoeB molybdopterin-synthase sulfur-carrier adenylyltransferase
moeB_moaD_adenylylation
Participant: Family: bacterial MoeB molybdopterin-synthase sulfur-carrier adenylyltransferase family
Family:
bacterial MoeB molybdopterin-synthase sulfur-carrier adenylyltransferase familyPANTHER:PTHR10953:SF194
Representative Members: PSEPK moeB exemplarUniProtKB:Q88PW3 Escherichia coli MoeB exemplarUniProtKB:P12282

Function

molybdopterin-synthase adenylyltransferase activityGO:0061605
Substrates: MoaD sulfur carrier with a C-terminal glycine ATP
Products: adenylylated MoaD C terminus diphosphate

Activates the MoaD C terminus for thiocarboxylate formation.

file:interpro/panther/PTHR10953/PTHR10953-entries.csv
The local PANTHER export contains E. coli MoeB P12282 in adenylyltransferase subfamily PTHR10953:SF194.
file:PSEPK/moeB/moeB-ai-review.yaml
The curated KT2440 review accepts GO:0061605 for Q88PW3 and rejects broader sulfurtransferase interpretations.
MoaD molybdopterin-synthase sulfur carrier
moaD_sulfur_carrier
Participant: Family: bacterial MoaD molybdopterin-synthase sulfur-carrier family
Family:
bacterial MoaD molybdopterin-synthase sulfur-carrier familyPANTHER:PTHR33359:SF1
Representative Members: PSEPK moaD exemplarUniProtKB:Q88NB9 Escherichia coli MoaD exemplarUniProtKB:P30748

Accepts activation at its C-terminal glycine and carries sulfur as a thiocarboxylate.

file:interpro/panther/PTHR33359/PTHR33359-entries.csv
The local PANTHER export contains E. coli MoaD P30748 in sulfur-carrier subfamily PTHR33359:SF1.
file:PSEPK/moaD/moaD-ai-review.yaml
The curated KT2440 review identifies Q88NB9 as the MoaD sulfur-carrier subunit of molybdopterin synthase.
Part 2: sulfur insertion into cPMP
MoaD-MoaE molybdopterin synthesisReactionmoaDE_mpt_synthesis

Annotons

MoaD2-MoaE2 molybdopterin synthase complex
moaDE_mpt_synthase_complex
Participant: Protein Complex: prokaryotic MoaD2-MoaE2 molybdopterin synthase complex
Protein Complex:
prokaryotic MoaD2-MoaE2 molybdopterin synthase complexGO:1990140 Conserved heterotetramer containing two MoaE catalytic subunits and two thiocarboxylated MoaD sulfur-carrier subunits.
Active units:
MoaE catalytic subunits2 per heterotetramer
Participant: Ortholog Of: PSEPK MoaE
Ortholog Of:
PSEPK MoaEUniProtKB:Q88NB8 Orthologs of the curated Pseudomonas putida KT2440 moaE/PP_1294 enzyme.
Role: Catalytic subunits that bind cPMP and receive sulfur from the paired MoaD C termini.
Function:
molybdopterin synthase activityGO:0030366
file:PSEPK/moaE/moaE-ai-review.yaml
The curated KT2440 review accepts molybdopterin synthase activity for Q88NB8.
MoaD sulfur-carrier subunits2 per heterotetramer
Participant: Family: prokaryotic MoaD molybdopterin synthase sulfur-carrier family
Family:
prokaryotic MoaD molybdopterin synthase sulfur-carrier familyPANTHER:PTHR33359:SF1
Representative Members: PSEPK moaD exemplarUniProtKB:Q88NB9 Escherichia coli MoaD exemplarUniProtKB:P30748
Role: Thiocarboxylated sulfur-carrier subunits that donate the two dithiolene sulfurs.
file:PSEPK/moaD/moaD-ai-review.yaml
The curated KT2440 review places Q88NB9 in the MoaD-MoaE molybdopterin synthase complex GO:1990140.

Function

molybdopterin synthase activityGO:0030366
Substrates: cyclic pyranopterin monophosphate (cPMP) two sulfur equivalents carried by the MoaD thiocarboxylates
Products: molybdopterin (MPT) two discharged MoaD sulfur carriers

The required MoaD2-MoaE2 complex incorporates two sulfur equivalents into cPMP to form the molybdopterin dithiolene.

file:interpro/panther/PTHR23404/PTHR23404-entries.csv
The local PANTHER export contains E. coli MoaE P30749 as a molybdopterin synthase catalytic subunit.
file:interpro/panther/PTHR33359/PTHR33359-entries.csv
The local PANTHER export contains E. coli MoaD P30748 in sulfur-carrier subfamily PTHR33359:SF1.
file:PSEPK/moaE/moaE-ai-review.yaml
The curated KT2440 review accepts molybdopterin synthase activity for Q88NB8.
file:PSEPK/moaD/moaD-ai-review.yaml
The curated KT2440 review places Q88NB9 in the MoaD-MoaE molybdopterin synthase complex GO:1990140.
Part 3: MPT adenylylation and molybdate insertion
Mo-molybdopterin formationMetabolic Pathwaymo_mpt_formation

Across prokaryotes, MPT is first adenylylated by a separate bacterial MogA or a catalytically competent prokaryotic MoaB and then loaded with molybdate by MoeA.

Connections

mpt_adenylylation -> molybdate_insertion Provides Input For
Adenylyl-MPT produced by the selected activation variant is the substrate for molybdate insertion.
Part 1: MPT adenylylation
Molybdopterin adenylylationReactionmpt_adenylylation
Variant set: MPT adenylyltransferase implementations by prokaryotic enzyme lineage (One Or More)
Separate MogA adenylyltransferaseReactionmogA_variant

Annotons

MogA molybdopterin adenylyltransferase
mogA_mpt_adenylyltransferase
Participant: Family: bacterial MogA molybdopterin adenylyltransferase family
Family:
bacterial MogA molybdopterin adenylyltransferase familyPANTHER:PTHR43764:SF1 MogA-family MPT adenylyltransferases; no exact KT2440 representative was found in this family.
Representative Members: Escherichia coli MogA exemplarUniProtKB:P0AF03

Function

molybdopterin adenylyltransferase activityGO:0061598
Substrates: molybdopterin (MPT) ATP
Products: adenylyl-molybdopterin diphosphate

Activates MPT for molybdate insertion.

file:interpro/panther/PTHR43764/PTHR43764-entries.csv
The local PANTHER export contains E. coli MogA P0AF03 as a molybdopterin adenylyltransferase.
Catalytically competent prokaryotic MoaB adenylyltransferaseReactionactive_moaB_variant

Annotons

Catalytically competent prokaryotic MoaB molybdopterin adenylyltransferase
active_moaB_mpt_adenylyltransferase
Participant: Ortholog Of: Pyrococcus furiosus MoaB
Ortholog Of:
Pyrococcus furiosus MoaBUniProtKB:Q8U3T3
Restricted to prokaryotic MoaB lineages with demonstrated or independently supported catalytic activity.

Function

molybdopterin adenylyltransferase activityGO:0061598
Substrates: molybdopterin (MPT) ATP
Products: adenylyl-molybdopterin diphosphate

Provides the MogA-equivalent reaction only in catalytically competent prokaryotic MoaB lineages.

file:interpro/panther/PTHR43232/PTHR43232-entries.csv
The local PANTHER export identifies P. furiosus MoaB Q8U3T3 as a molybdopterin adenylyltransferase.
Part 2: molybdate insertion into adenylyl-MPT
Molybdopterin molybdotransferReactionmolybdate_insertion

Annotons

MoeA molybdopterin molybdotransferase
moeA_molybdotransferase
Participant: Ortholog Of: PSEPK MoeA
Ortholog Of:
PSEPK MoeAUniProtKB:Q88L14 Orthologs of the curated Pseudomonas putida KT2440 moeA/PP_2123 enzyme.

Function

molybdopterin molybdotransferase activityGO:0061599
Substrates: adenylyl-molybdopterin molybdate
Products: Mo-molybdopterin (Mo-MPT) AMP

Inserts molybdate into activated MPT.

file:interpro/panther/PTHR10192/PTHR10192-entries.csv
The local PANTHER export contains E. coli MoeA P12281 as a molybdopterin molybdenumtransferase.
file:PSEPK/moeA/moeA-ai-review.yaml
The curated KT2440 review accepts molybdopterin molybdotransferase activity for Q88L14.
Part 4: optional nucleotide maturation of Mo-MPT (optional)
Optional Mo-MPT nucleotide maturationMetabolic Pathwaynucleotide_maturation

A realization may retain Mo-MPT or append guanine and/or cytosine nucleotides for compatible client classes.

Variant set: Mo-MPT dinucleotide variants by appended nucleotide (Zero Or More)
MGD formation by MobAReactionmgd_variant

Annotons

MobA molybdenum cofactor guanylyltransferase
mobA_mgd_synthesis
Participant: Family: bacterial MobA molybdenum cofactor guanylyltransferase family
Family:
bacterial MobA molybdenum cofactor guanylyltransferase familyPANTHER:PTHR19136:SF81
Representative Members: PSEPK mobA exemplarUniProtKB:Q88HA3 Escherichia coli MobA exemplarUniProtKB:P32173

Function

molybdenum cofactor guanylyltransferase activityGO:0061603
Substrates: Mo-molybdopterin (Mo-MPT) GTP
Products: Mo-molybdopterin guanine dinucleotide (MGD) diphosphate

Produces the guanine-dinucleotide cofactor variant.

file:interpro/panther/PTHR19136/PTHR19136-entries.csv
The local PANTHER export contains PSEPK Q88HA3 and E. coli P32173 in guanylyltransferase subfamily PTHR19136:SF81.
file:PSEPK/mobA/mobA-ai-review.yaml
The curated KT2440 review accepts molybdenum cofactor guanylyltransferase activity for Q88HA3.
MCD formation by MocAReactionmcd_variant

Annotons

MocA molybdenum cofactor cytidylyltransferase
mocA_mcd_synthesis
Participant: Family: bacterial MocA molybdenum cofactor cytidylyltransferase family
Family:
bacterial MocA molybdenum cofactor cytidylyltransferase familyPANTHER:PTHR43777:SF1 MocA proteins supported by orthology and subfamily context; the broader PTHR43777 family also contains non-MocA proteins.
Representative Members: PSEPK PP_2483 predicted MocA exemplarUniProtKB:Q88K10 PSEPK PP_4230 predicted MocA exemplarUniProtKB:Q88F68 Escherichia coli MocA exemplarUniProtKB:Q46810

Function

molybdenum cofactor cytidylyltransferase activityGO:0061602
Substrates: Mo-molybdopterin (Mo-MPT) CTP
Products: Mo-molybdopterin cytosine dinucleotide (MCD) diphosphate

Produces the cytosine-dinucleotide cofactor variant.

file:PSEPK/moaA/moaA-bioinformatics/mob_like_kegg_orthology.tsv
The reproducible KEGG lookup maps both PSEPK Q88K10/PP_2483 and Q88F68/PP_4230 to MocA orthology K07141.
file:interpro/panther/PTHR43777/PTHR43777-entries.csv
The local PANTHER export contains E. coli MocA Q46810 in PTHR43777:SF1; broader family membership alone is not treated as sufficient.
file:PSEPK/PP_2483/PP_2483-ai-review.yaml
The curated KT2440 review supports GO:0061602 as a predicted replacement for the broad Q88K10 nucleotidyltransferase annotation.
file:PSEPK/PP_4230/PP_4230-ai-review.yaml
The curated KT2440 review supports GO:0061602 as a predicted replacement for the broad Q88F68 nucleotidyltransferase annotation.