De novo biotin biosynthesis via the BioC-BioH route

Bacterial de novo biotin synthesis in which BioC methylates malonyl-ACP, shared fatty-acid-synthase reactions extend the masked intermediate to pimeloyl-ACP methyl ester, and BioH removes the methyl group. BioF, BioA, BioD, and BioB then assemble the two-ring biotin cofactor. The module models the six pathway-specific enzymes; generic fatty-acid elongation machinery is an explicit dependency rather than a biotin-specific member, and biotin attachment and BirA-mediated regulation are outside the biosynthesis boundary.

MODULE:biotin_biosynthesisDRAFTMetabolic Pathwaymodules/biotin_biosynthesis.yaml
biotin biosynthetic processGO:0009102
KEGG:ppu00780
Pseudomonas putida KT2440 biotin metabolism
The PSEPK pathway bucket contains the bioBFHCD cluster and the separate bioA gene, together with generic fatty-acid and biotin-utilization genes that require boundary curation.
GO:0009102
biotin biosynthetic process
The module is grounded in the GO biological-process term for biotin synthesis.
file:projects/P_PUTIDA/deep-research/PSEPK__biotin_biosynthesis__ppu00780-deep-research-openscientist.md
OpenScientist module/pathway/taxon report for PSEPK biotin biosynthesis
Supports coverage of all six pathway-specific reactions, exclusion of BirA and generic fatty-acid-synthesis proteins from dedicated membership, and complete pathway satisfiability in KT2440. Individual enzyme assignments remain homology- and genomic-context-based rather than direct KT2440 biochemical evidence.
file:projects/P_PUTIDA/data/psepk_pathway_membership.tsv
PSEPK pathway membership table
Supplies exact locus, gene-symbol, accession, and pathway-bucket mappings used for the PSEPK satisfiability pass.
7Nodes
6Parts
0Variant Sets
0Variants
6Annotons
5Connections

Derived QC

Recommended-field compliance

55.6% recommended fields populated
  • module.knowledge_gaps[0] · status (0/1)
  • module.knowledge_gaps[0] · provenance (0/1)
  • module.knowledge_gaps[1] · status (0/1)
  • module.knowledge_gaps[1] · provenance (0/1)

Module deep research

✗ none found

No MODULE:biotin_biosynthesis deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • bioC_step → bioH_step [NOT_CHECKED]
    Shared fatty-acid-synthase reactions perform two elongation cycles between the BioC and BioH pathway-specific control points.
  • bioH_step → bioF_step [NOT_CHECKED]
  • bioF_step → bioA_step [NOT_CHECKED]
  • bioA_step → bioD_step [NOT_CHECKED]
  • bioD_step → bioB_step [NOT_CHECKED]

Gene-review completeness (6/6 grounded genes reviewed)

6 complete review(s) · 5 with deep research · 0 missing review · 1 reviewed but lacking deep research

Gene Review Complete Deep research
bioA Q88D44 ✓ ✓ ✗
bioB Q88QX2 ✓ ✓ ✓
bioC Q88QW9 ✓ ✓ ✓
bioD Q88QW8 ✓ ✓ ✓
bioF Q88QX1 ✓ ✓ ✓
bioH Q88QX0 ✓ ✓ ✓

Details

de novo biotin biosynthesisMetabolic Pathwaybiotin_biosynthesis
biotin biosynthetic processGO:0009102

This reusable module contains six substantive pathway-specific enzyme parts. BirA-mediated biotin attachment and transcriptional regulation are part of the broader biotin cycle, not de novo cofactor synthesis. Molecular functions are attached only to leaf annotons, every leaf has an exact PSEPK UniProt exemplar, and no cytoplasmic location is repeated at module level.

Connections

bioC_step -> bioH_step Precedes
bioH_step -> bioF_step Precedes
bioF_step -> bioA_step Precedes
bioA_step -> bioD_step Precedes
bioD_step -> bioB_step Precedes
Part 1: malonyl-ACP carboxyl methylation
Malonyl-ACP to malonyl-ACP methyl esterReactionbioC_step

Annotons

BioC malonyl-ACP O-methyltransferase
bioC_activity
Participant: Family: BioC malonyl-ACP O-methyltransferase family
Family:
BioC malonyl-ACP O-methyltransferase familyNCBIfam:TIGR02072
Representative Members: PSEPK BioCUniProtKB:Q88QW9
Required Function:
malonyl-ACP O-methyltransferase activityGO:0102130

Function

malonyl-ACP O-methyltransferase activityGO:0102130
Substrates: malonyl-[acyl-carrier protein] S-adenosyl-L-methionine
Products: malonyl-[acyl-carrier protein] methyl ester S-adenosyl-L-homocysteine

Masks the free carboxyl group so the pimelate precursor can be assembled by the shared fatty-acid-synthase elongation cycle.

Part 2: pathway-specific ester unmasking
Pimeloyl-ACP methyl ester to pimeloyl-ACPReactionbioH_step

Annotons

BioH pimeloyl-ACP methyl ester esterase
bioH_activity
Participant: Family: BioH pimeloyl-ACP methyl ester esterase family
Family:
BioH pimeloyl-ACP methyl ester esterase familyPANTHER:PTHR43194:SF5
Representative Members: PSEPK BioHUniProtKB:Q88QX0
Required Function:
pimeloyl-ACP methyl ester esterase activityGO:0090499

Function

pimeloyl-ACP methyl ester esterase activityGO:0090499
Substrates: pimeloyl-[acyl-carrier protein] methyl ester water
Products: pimeloyl-[acyl-carrier protein] methanol

Releases the free pimeloyl-ACP carboxyl group after the shared elongation machinery has generated the seven-carbon precursor.

Part 3: 8-amino-7-oxononanoate formation
Pimeloyl-ACP to 8-amino-7-oxononanoateReactionbioF_step

Annotons

BioF 8-amino-7-oxononanoate synthase
bioF_activity
Participant: Family: proteobacterial BioF family
Family:
proteobacterial BioF familyNCBIfam:TIGR00858
Representative Members: PSEPK BioFUniProtKB:Q88QX1
Required Function:
8-amino-7-oxononanoate synthase activityGO:0008710

Function

8-amino-7-oxononanoate synthase activityGO:0008710
Substrates: pimeloyl-[acyl-carrier protein] L-alanine
Products: 8-amino-7-oxononanoate holo-[acyl-carrier protein] carbon dioxide
Cofactors: pyridoxal 5'-phosphate

Commits the pimelate precursor to biotin ring assembly through a PLP-dependent decarboxylative condensation with L-alanine.

Part 4: 7,8-diaminononanoate formation
8-amino-7-oxononanoate to 7,8-diaminononanoateReactionbioA_step

Annotons

BioA adenosylmethionine aminotransferase
bioA_activity
Participant: Family: BioA aminotransferase family
Family:
BioA aminotransferase familyNCBIfam:TIGR00508
Representative Members: PSEPK BioAUniProtKB:Q88D44
Required Function:
adenosylmethionine-8-amino-7-oxononanoate transaminase activityGO:0004015

Function

adenosylmethionine-8-amino-7-oxononanoate transaminase activityGO:0004015
Substrates: 8-amino-7-oxononanoate S-adenosyl-L-methionine
Products: 7,8-diaminononanoate S-adenosyl-4-methylsulfanyl-2-oxobutanoate
Cofactors: pyridoxal 5'-phosphate

Supplies the second amino group needed to close the ureido ring.

Part 5: dethiobiotin ring closure
7,8-diaminononanoate to dethiobiotinReactionbioD_step

Annotons

BioD dethiobiotin synthase
bioD_activity
Participant: Family: BioD dethiobiotin synthase family
Family:
BioD dethiobiotin synthase familyNCBIfam:TIGR00347
Representative Members: PSEPK BioDUniProtKB:Q88QW8
Required Function:
dethiobiotin synthase activityGO:0004141

Function

dethiobiotin synthase activityGO:0004141
Substrates: 7,8-diaminononanoate carbon dioxide ATP
Products: dethiobiotin ADP phosphate
Cofactors: magnesium ion

ATP-dependent carboxylation and closure of the ureido ring.

Part 6: sulfur insertion and biotin formation
Dethiobiotin to biotinReactionbioB_step

Annotons

BioB biotin synthase
bioB_activity
Participant: Family: BioB radical-SAM biotin synthase family
Family:
BioB radical-SAM biotin synthase familyNCBIfam:TIGR00433
Representative Members: PSEPK BioBUniProtKB:Q88QX2
Required Function:
biotin synthase activityGO:0004076

Function

biotin synthase activityGO:0004076
Substrates: dethiobiotin sulfur donor S-adenosyl-L-methionine reducing equivalents
Products: biotin 5'-deoxyadenosine L-methionine
Cofactors: 4 iron, 4 sulfur cluster 2 iron, 2 sulfur cluster

Inserts sulfur into dethiobiotin through radical-SAM chemistry to complete the biotin cofactor.