Pantoate-derived coenzyme A biosynthesis

Synthesis of coenzyme A (CoA) from pantoate and beta-alanine. The pantoate branch transfers a hydroxymethyl group to 3-methyl-2-oxobutanoate, reduces 2-dehydropantoate to (R)-pantoate, and reaches 4'-phosphopantothenate by one of two reaction-order variants. Bacteria and eukaryotes generally use PanC to form pantothenate and then one of three unrelated pantothenate kinase families. Most archaea instead phosphorylate pantoate with PoK before PPS condenses 4-phosphopantoate with beta-alanine, so free pantothenate is not an intermediate. Four subsequent reactions add and decarboxylate cysteine, adenylylate 4'-phosphopantetheine, and phosphorylate dephospho-CoA. CoaB and CoaC may be separate or fused, and the final CoaD and CoaE activities may be separate or fused in CoA synthase. Beta-alanine supply is an upstream dependency because organisms use different routes, including PanD-dependent aspartate decarboxylation, pyrimidine degradation, and uptake. CoA salvage, phosphopantetheine release from acyl carrier proteins, and downstream CoA-dependent metabolism are outside the module boundary.

MODULE:coenzyme_a_biosynthesisDRAFTMetabolic Pathwaymodules/coenzyme_a_biosynthesis.yaml
pantothenate biosynthetic processGO:0015940 coenzyme A biosynthetic processGO:0015937
GO:0015940
pantothenate biosynthetic process
Grounds the canonical PanC branch that forms pantothenate from pantoate and beta-alanine before phosphorylation.
GO:0015937
coenzyme A biosynthetic process
Grounds conversion of pantoate-derived intermediates to CoA through convergence at 4'-phosphopantothenate.
KEGG:ppu00770
Pseudomonas putida KT2440 pantothenate and CoA biosynthesis map
Grounds the PSEPK pathway instance and its exact PanB, PanC, PanE-like, CoaX, CoaBC, CoaD, and CoaE candidates. Broad map membership is not used by itself to promote salvage or pyrimidine-catabolism proteins into this reaction chain.
PMID:26913973
The revisited genome of Pseudomonas putida KT2440 enlightens its value as a robust metabolic chassis.
The KT2440 genome reannotation supports reductive pyrimidine degradation as a source of beta-alanine. This resolves substrate supply without inventing a PanD ortholog or making pyrimidine catabolism a core part of the reusable module.
file:projects/P_PUTIDA/data/psepk_pathway_membership.tsv
PSEPK pathway membership table
Provides accession and locus mappings used for the PSEPK satisfiability check and exposes broad KEGG spillover that requires manual boundary review.
file:projects/P_PUTIDA/deep-research/PSEPK__coenzyme_a_biosynthesis__ppu00770-deep-research-openscientist.md
OpenScientist PSEPK module, pathway, and taxon synthesis
Species-aware retrieval used to assess paralog candidates, beta-alanine supply, and the distinction between biosynthesis and salvage mappings.
file:modules/coenzyme_a_biosynthesis-deep-research-openscientist.md
OpenScientist generic pantoate-derived CoA biosynthesis synthesis
Confirms the conserved reaction boundary, enzyme-architecture variants, and the archaeal PoK/PPS route that reverses the order of beta-alanine condensation and phosphorylation before convergence at 4'-phosphopantothenate.
file:human/PPCS/PPCS-ai-review.yaml
Human PPCS gene review
Grounds the standalone ATP-preferring phosphopantothenate--cysteine ligase implementation.
file:human/PPCDC/PPCDC-ai-review.yaml
Human PPCDC gene review
Grounds the standalone phosphopantothenoylcysteine decarboxylase implementation.
file:human/COASY/COASY-ai-review.yaml
Human COASY gene review
Grounds the fused PPAT and dephospho-CoA kinase implementation.
file:PSEPK/panB/panB-ai-review.yaml
PSEPK PanB gene review
Grounds the bacterial ketopantoate-hydroxymethyltransferase implementation.
file:PSEPK/panE/panE-ai-review.yaml
PSEPK PanE gene review
Grounds the canonical bacterial ketopantoate-reductase implementation.
file:PSEPK/panC/panC-ai-review.yaml
PSEPK PanC gene review
Grounds the bacterial pantothenate-synthetase implementation.
file:PSEPK/coaX/coaX-ai-review.yaml
PSEPK CoaX gene review
Grounds the bacterial type III pantothenate kinase implementation.
file:PSEPK/dfp/dfp-ai-review.yaml
PSEPK CoaBC gene review
Grounds the fused bacterial CoaB and CoaC implementation.
file:PSEPK/coaD/coaD-ai-review.yaml
PSEPK CoaD gene review
Grounds the standalone bacterial phosphopantetheine adenylyltransferase implementation.
file:PSEPK/coaE/coaE-ai-review.yaml
PSEPK CoaE gene review
Grounds the standalone bacterial dephospho-CoA kinase implementation.
21Nodes
11Parts
4Variant Sets
9Variants
14Annotons
8Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

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

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (13/24 grounded genes reviewed)

13 complete review(s) · 7 with deep research · 11 missing review · 6 reviewed but lacking deep research

Gene Review Complete Deep research
coaD Q88CQ7 ✓ ✓ ✓
coaE Q88Q65 ✓ ✓ ✓
COASY Q13057 ✓ ✓ ✗
coaX Q88QQ0 ✓ ✓ ✓
dfp Q88C96 ✓ ✓ ✓
Escherichia coli CoaA P0A6I3 ✗ — —
Escherichia coli CoaD P0A6I6 ✗ — —
Escherichia coli CoaE P0A6I9 ✗ — —
Escherichia coli PanE P0A9J4 ✗ — —
Escherichia coli CoaBC P0ABQ0 ✗ — —
Escherichia coli PanB P31057 ✗ — —
Escherichia coli PanC P31663 ✗ — —
Mycobacterium tuberculosis CoaX P9WPA1 ✗ — —
panB Q88DW9 ✓ ✓ ✓
panC Q88DW8 ✓ ✓ ✓
panE Q88N64 ✓ ✓ ✓
PANK1 Q8TE04 ✓ ✓ ✗
PANK2 Q9BZ23 ✓ ✓ ✗
PANK3 Q9H999 ✓ ✓ ✗
PPCDC Q96CD2 ✓ ✓ ✗
PPCS Q9HAB8 ✓ ✓ ✗
Thermococcus kodakarensis PoK Q5JHF1 ✗ — —
Thermococcus kodakarensis PPS Q5JIZ8 ✗ — —
Pseudomonas aeruginosa PanE Q9HW09 ✗ — —

Details

Pantoate-derived coenzyme A biosynthesisMetabolic Pathwaycoenzyme_a_biosynthesis
pantothenate biosynthetic processGO:0015940 coenzyme A biosynthetic processGO:0015937

The module models eight reaction activities in either complete route and keeps molecular functions on leaf annotons. It intentionally has no module-level cellular location: bacterial and archaeal enzymes are commonly cytosolic, whereas eukaryotic isoforms and fused CoA synthases can occupy different compartments. Family selectors identify established catalytic implementations, while the required molecular function remains the decisive criterion. Related reductase families should not satisfy the pantoate step without substrate-specific evidence. Taxon-specific precursor sources, paralogs, and pathway-map spillover belong in pathway-instance reviews rather than this module.

Connections

PanB supplies 2-dehydropantoate to the PanE-like reductase.
The reductase supplies (R)-pantoate to either the PanC/PanK route or the archaeal PoK/PPS route.
Both route variants converge on 4'-phosphopantothenate, which is then conjugated with cysteine.
Phosphopantothenoylcysteine is decarboxylated to phosphopantetheine.
4'-phosphopantetheine is adenylylated to dephospho-CoA.
Dephospho-CoA is phosphorylated to coenzyme A.
Part 1: 2-dehydropantoate formation
3-methyl-2-oxobutanoate to 2-dehydropantoateReactionketopantoate_hydroxymethyltransferase_step

Annotons

PanB ketopantoate hydroxymethyltransferase
panB_activity
Participant: Family: PanB family
Family:
PanB familyPANTHER:PTHR20881
Representative Members: PSEPK PanBUniProtKB:Q88DW9 Escherichia coli PanBUniProtKB:P31057
Required Function:
3-methyl-2-oxobutanoate hydroxymethyltransferase activityGO:0003864

Function

3-methyl-2-oxobutanoate hydroxymethyltransferase activityGO:0003864
Substrates: 3-methyl-2-oxobutanoate 5,10-methylenetetrahydrofolate water
Products: 2-dehydropantoate tetrahydrofolate

Produces the keto precursor of pantoate.

Part 2: pantoate formation
2-dehydropantoate to (R)-pantoateReactionketopantoate_reductase_step

Annotons

PanE-like ketopantoate reductase
panE_activity
Participant: Family: canonical PanE ketopantoate reductase family
Family:
canonical PanE ketopantoate reductase familyPANTHER:PTHR43765
Representative Members: PSEPK PanEUniProtKB:Q88N64 Escherichia coli PanEUniProtKB:P0A9J4 Pseudomonas aeruginosa PanEUniProtKB:Q9HW09
Required Function:
2-dehydropantoate 2-reductase activityGO:0008677

Function

2-dehydropantoate 2-reductase activityGO:0008677
Substrates: 2-dehydropantoate NADPH proton
Products: (R)-pantoate NADP+

Reduces ketopantoate to pantoate. Related reductase paralogs do not satisfy this step without substrate-specific evidence.

Part 3: formation of 4'-phosphopantothenate
Pantoate and beta-alanine to 4'-phosphopantothenateMetabolic Pathwaypantoate_to_phosphopantothenate_routes

Two taxon-dependent two-reaction routes converge on 4'-phosphopantothenate. The canonical route forms free pantothenate before phosphorylation, whereas the archaeal route phosphorylates pantoate before beta-alanine condensation.

Variant set: Routes to 4'-phosphopantothenate by taxon-dependent reaction order (Exactly One)
Canonical PanC then pantothenate kinase routeMetabolic Pathwaycanonical_panc_pank_route

The bacterial and eukaryotic route forms pantothenate with PanC and then phosphorylates it with a type I, II, or III pantothenate kinase.

Connections

Pantothenate formed by PanC is the substrate for the selected type I, II, or III pantothenate kinase.
Part 1: pantothenate formation
(R)-pantoate and beta-alanine to pantothenateReactionpantothenate_synthetase_step

Annotons

PanC pantothenate synthetase
panC_activity
Participant: Family: PanC pantothenate synthetase family
Family:
PanC pantothenate synthetase familyPANTHER:PTHR21299
Representative Members: PSEPK PanCUniProtKB:Q88DW8 Escherichia coli PanCUniProtKB:P31663
Required Function:
pantoate-beta-alanine ligase activityGO:0004592

Function

pantoate-beta-alanine ligase activityGO:0004592
Substrates: (R)-pantoate beta-alanine ATP
Products: (R)-pantothenate AMP diphosphate

Produces pantothenate. Beta-alanine is an input supplied by a taxon-dependent upstream route and is not assigned to PanD by default.

Part 2: pantothenate phosphorylation
Pantothenate to 4'-phosphopantothenateReactionpantothenate_kinase_step

Unrelated type I, type II, and type III pantothenate kinase families catalyze the same first committed reaction of CoA synthesis.

Variant set: Pantothenate kinase family variants by enzyme family (One Or More)
Type I bacterial CoaA implementationReactiontype_i_pantothenate_kinase_variant

Annotons

Type I pantothenate kinase
coaA_activity
Participant: Family: type I pantothenate kinase family
Family:
type I pantothenate kinase familyPANTHER:PTHR10285
Representative Members: Escherichia coli CoaAUniProtKB:P0A6I3
Required Function:
pantothenate kinase activityGO:0004594

Function

pantothenate kinase activityGO:0004594
Substrates: (R)-pantothenate ATP
Products: (R)-4'-phosphopantothenate ADP

Common bacterial type I kinase implementation.

Type II eukaryotic PANK implementationReactiontype_ii_pantothenate_kinase_variant

Annotons

Type II pantothenate kinase
pank_activity
Participant: Family: type II pantothenate kinase family
Family:
type II pantothenate kinase familyPANTHER:PTHR12280
Representative Members: Human PANK1UniProtKB:Q8TE04 Human PANK2UniProtKB:Q9BZ23 Human PANK3UniProtKB:Q9H999
Required Function:
pantothenate kinase activityGO:0004594

Function

pantothenate kinase activityGO:0004594
Substrates: (R)-pantothenate ATP
Products: (R)-4'-phosphopantothenate ADP

Eukaryotic type II kinase implementation.

Type III bacterial CoaX implementationReactiontype_iii_pantothenate_kinase_variant

Annotons

Type III pantothenate kinase
coaX_activity
Participant: Family: type III pantothenate kinase family
Family:
type III pantothenate kinase familyPANTHER:PTHR34265
Representative Members: PSEPK CoaXUniProtKB:Q88QQ0 Mycobacterium tuberculosis CoaXUniProtKB:P9WPA1
Required Function:
pantothenate kinase activityGO:0004594

Function

pantothenate kinase activityGO:0004594
Substrates: (R)-pantothenate ATP
Products: (R)-4'-phosphopantothenate ADP

Bacterial type III kinase implementation.

Archaeal PoK then PPS routeMetabolic Pathwayarchaeal_pok_pps_route

The route used by most archaea phosphorylates pantoate before beta-alanine condensation and therefore bypasses free pantothenate.

Connections

The 4-phosphopantoate made by PoK is the direct substrate for PPS.
Part 1: pantoate phosphorylation
Pantoate to 4-phosphopantoateReactionpantoate_kinase_step

Annotons

Archaeal pantoate kinase
pok_activity
Participant: Family: archaeal pantoate kinase family
Family:
archaeal pantoate kinase familyPANTHER:PTHR42282:SF1
Representative Members: Thermococcus kodakarensis PoKUniProtKB:Q5JHF1
Required Function:
kinase activityGO:0016301

Function

pantoate kinase activityGO:0016301
Substrates: (R)-pantoate ATP
Products: (R)-4-phosphopantoate ADP proton

Produces 4-phosphopantoate before beta-alanine is incorporated.

Part 2: phosphopantothenate formation
4-phosphopantoate and beta-alanine to 4'-phosphopantothenateReactionphosphopantothenate_synthetase_step

Annotons

Archaeal phosphopantothenate synthetase
pps_activity
Participant: Family: archaeal phosphopantothenate synthetase family
Family:
archaeal phosphopantothenate synthetase familyPANTHER:PTHR40695:SF1
Representative Members: Thermococcus kodakarensis PPSUniProtKB:Q5JIZ8
Required Function:
acid-amino acid ligase activityGO:0016881

Function

4-phosphopantoate--beta-alanine ligase activityGO:0016881
Substrates: (R)-4-phosphopantoate beta-alanine ATP
Products: (R)-4'-phosphopantothenate AMP diphosphate proton

Condenses 4-phosphopantoate with beta-alanine to reach the common phosphopantothenate intermediate.

Part 4: phosphopantothenoylcysteine synthesis
4'-phosphopantothenate to phosphopantothenoylcysteineReactionphosphopantothenoylcysteine_ligase_step

The ligase can be a standalone PPCS protein or the CoaB domain of a fused bacterial CoaBC protein; nucleotide preference is family dependent.

Variant set: Phosphopantothenate--cysteine ligase architectures by protein architecture (One Or More)
Standalone PPCS implementationReactionstandalone_ppcs_variant

Annotons

Standalone phosphopantothenate--cysteine ligase
ppcs_activity
Participant: Family: PPCS family
Family:
PPCS familyPANTHER:PTHR12290
Representative Members: Human PPCSUniProtKB:Q9HAB8
Required Function:
phosphopantothenate--cysteine ligase activityGO:0004632

Function

phosphopantothenate--cysteine ligase activityGO:0004632
Substrates: (R)-4'-phosphopantothenate L-cysteine ATP
Products: phosphopantothenoyl-L-cysteine AMP diphosphate

Standalone, ATP-preferring PPCS implementation.

Fused bacterial CoaB implementationReactionfused_coaB_variant

Annotons

CoaB domain of bifunctional CoaBC
coaB_activity
Participant: Family: bifunctional CoaBC family
Family:
bifunctional CoaBC familyNCBIfam:TIGR00521
Representative Members: PSEPK CoaBCUniProtKB:Q88C96 Escherichia coli CoaBCUniProtKB:P0ABQ0
Required Function:
phosphopantothenate--cysteine ligase activityGO:0004632

Function

phosphopantothenate--cysteine ligase activityGO:0004632
Substrates: (R)-4'-phosphopantothenate L-cysteine CTP
Products: phosphopantothenoyl-L-cysteine CMP diphosphate

C-terminal CoaB domain of fused bacterial CoaBC.

Part 5: phosphopantetheine formation
Phosphopantothenoylcysteine to 4'-phosphopantetheineReactionphosphopantothenoylcysteine_decarboxylase_step

Annotons

Phosphopantothenoylcysteine decarboxylase
ppcdc_activity
Participant: Family: phosphopantothenoylcysteine decarboxylase family
Family:
phosphopantothenoylcysteine decarboxylase familyPANTHER:PTHR14359
Representative Members: Human PPCDCUniProtKB:Q96CD2 PSEPK CoaBCUniProtKB:Q88C96 Escherichia coli CoaBCUniProtKB:P0ABQ0
Required Function:
phosphopantothenoylcysteine decarboxylase activityGO:0004633

Function

phosphopantothenoylcysteine decarboxylase activityGO:0004633
Substrates: phosphopantothenoyl-L-cysteine proton
Products: (R)-4'-phosphopantetheine carbon dioxide

Produces 4'-phosphopantetheine; the activity can reside in a standalone PPCDC or the CoaC domain of fused CoaBC.

Part 6: dephospho-CoA formation
4'-phosphopantetheine to dephospho-CoAReactionphosphopantetheine_adenylyltransferase_step

The adenylyltransferase can be a standalone bacterial CoaD or one domain of a fused eukaryotic CoA synthase.

Variant set: Phosphopantetheine adenylyltransferase architectures by protein architecture (One Or More)
Standalone bacterial CoaD implementationReactionstandalone_coaD_variant

Annotons

Standalone phosphopantetheine adenylyltransferase
coaD_activity
Participant: Family: bacterial CoaD family
Family:
bacterial CoaD familyPANTHER:PTHR21342
Representative Members: PSEPK CoaDUniProtKB:Q88CQ7 Escherichia coli CoaDUniProtKB:P0A6I6
Required Function:
pantetheine-phosphate adenylyltransferase activityGO:0004595

Function

pantetheine-phosphate adenylyltransferase activityGO:0004595
Substrates: (R)-4'-phosphopantetheine ATP proton
Products: 3'-dephospho-CoA diphosphate

Standalone bacterial CoaD implementation.

Fused CoA synthase PPAT implementationReactionfused_coasy_ppat_variant

Annotons

PPAT domain of bifunctional CoA synthase
coasy_ppat_activity
Participant: Family: bifunctional CoA synthase family
Family:
bifunctional CoA synthase familyPANTHER:PTHR10695
Representative Members: Human COASYUniProtKB:Q13057
Required Function:
pantetheine-phosphate adenylyltransferase activityGO:0004595

Function

pantetheine-phosphate adenylyltransferase activityGO:0004595
Substrates: (R)-4'-phosphopantetheine ATP proton
Products: 3'-dephospho-CoA diphosphate

PPAT domain of fused eukaryotic CoA synthase.

Part 7: coenzyme A formation
Dephospho-CoA to coenzyme AReactiondephospho_coa_kinase_step

Annotons

Dephospho-CoA kinase
coaE_activity
Participant: Family: CoaE/CoA synthase kinase family
Family:
CoaE/CoA synthase kinase familyPANTHER:PTHR10695
Representative Members: PSEPK CoaEUniProtKB:Q88Q65 Escherichia coli CoaEUniProtKB:P0A6I9 Human COASYUniProtKB:Q13057
Required Function:
dephospho-CoA kinase activityGO:0004140

Function

dephospho-CoA kinase activityGO:0004140
Substrates: 3'-dephospho-CoA ATP
Products: coenzyme A ADP proton

Completes CoA synthesis; the activity can be a standalone CoaE or the kinase domain of bifunctional CoA synthase.