L-valine, L-leucine, and L-isoleucine biosynthesis

Microbial biosynthesis of the three branched-chain amino acids. L-isoleucine synthesis begins with threonine deamination to 2-oxobutanoate. The IlvI-IlvH acetohydroxy-acid synthase, IlvC ketol-acid reductoisomerase, and IlvD dihydroxy-acid dehydratase then form a shared catalytic trunk that processes either the valine precursor derived from two pyruvate molecules or the isoleucine precursor derived from pyruvate plus 2-oxobutanoate. The valine intermediate 2-oxoisovalerate also enters a three-reaction LeuA/LeuC-LeuD/LeuB extension branch. IlvE performs the terminal transamination for all three products. The module requires each biochemical step but allows any validated member of the biosynthetic threonine-deaminase family to satisfy the entry reaction.

MODULE:branched_chain_amino_acid_biosynthesisDRAFTMetabolic Pathwaymodules/branched_chain_amino_acid_biosynthesis.yaml
branched-chain amino acid biosynthetic processGO:0009082
GO:0009082
Branched-chain amino acid biosynthetic process
The module is grounded in the GO biological process for valine, leucine, and isoleucine biosynthesis.
KEGG:ppu00290
Pseudomonas putida KT2440 valine, leucine, and isoleucine biosynthesis
The PSEPK pathway instance supplies the candidate set for the species-level satisfiability pass; map spillover and paralogous enzyme families require manual boundary curation.
file:projects/P_PUTIDA/data/psepk_gene_list.tsv
PSEPK UniProt metadata table
Supplies the exact PSEPK accessions, locus tags, protein families, and pathway keywords used for the representative members below.
file:projects/P_PUTIDA/deep-research/PSEPK__branched_chain_amino_acid_biosynthesis__ppu00290-deep-research-openscientist.md
OpenScientist module/pathway/taxon report for PSEPK branched-chain amino-acid biosynthesis
Supports the six-part pathway boundary, coverage by the selected KT2440 proteins, and exclusion of broad-map and catabolic-family candidates. Individual assignments remain based on exact database records and orthology because the report found no target-strain enzymology for the proteins themselves; IlvA and additional AHAS-family paralog roles remain unresolved.
10Nodes
9Parts
0Variant Sets
0Variants
10Annotons
8Connections

Derived QC

Recommended-field compliance

77.8% recommended fields populated
  • module.knowledge_gaps[0] · provenance (0/1)
  • module.knowledge_gaps[1] · provenance (0/1)

Module deep research

✗ none found

No MODULE:branched_chain_amino_acid_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.

  • ilvA_step → ilvIH_step [NOT_CHECKED]
  • ilvIH_step → ilvC_step [NOT_CHECKED]
  • ilvC_step → ilvD_step [NOT_CHECKED]
  • ilvD_step → leucine_extension [NOT_CHECKED]
  • ilvD_step → ilvE_step [NOT_CHECKED]
  • leucine_extension → ilvE_step [NOT_CHECKED]

Gene-review completeness (11/11 grounded genes reviewed)

11 complete review(s) · 8 with deep research · 0 missing review · 3 reviewed but lacking deep research

Gene Review Complete Deep research
ilvA-I Q88HB4 ✓ ✓ ✓
ilvA-II Q88CN1 ✓ ✓ ✗
ilvC Q88DZ0 ✓ ✓ ✓
ilvD Q88CQ2 ✓ ✓ ✗
ilvE Q88H54 ✓ ✓ ✓
ilvH Q88DY9 ✓ ✓ ✓
ilvI Q88DY8 ✓ ✓ ✓
leuA Q88P28 ✓ ✓ ✗
leuB Q88LE5 ✓ ✓ ✓
leuC Q88LE8 ✓ ✓ ✓
leuD Q88LE7 ✓ ✓ ✓

Details

branched-chain amino acid biosynthesisMetabolic Pathwaybranched_chain_amino_acid_biosynthesis
branched-chain amino acid biosynthetic processGO:0009082

The PSEPK ppu00290 bucket also contains shorter serine/threonine dehydratases, two additional AHAS-like large subunits, AlaA, and leucine dehydrogenase. They are not counted as module members because pathway-map membership alone does not establish that they supply the physiological biosynthetic route.

Connections

ilvA_step -> ilvIH_step Precedes
ilvIH_step -> ilvC_step Precedes
ilvC_step -> ilvD_step Precedes
ilvD_step -> ilvE_step Precedes
Part 1: isoleucine-branch 2-oxobutanoate supply
L-threonine to 2-oxobutanoateReactionilvA_step

Annotons

Biosynthetic threonine deaminase
ilvA_activity
Participant: Family: full-length biosynthetic threonine deaminase family
Family:
full-length biosynthetic threonine deaminase familyInterPro:IPR005787
Representative Members: PSEPK IlvA-IUniProtKB:Q88HB4 PSEPK IlvA-IIUniProtKB:Q88CN1
Required Function:
threonine deaminase activityGO:0004794

Function

threonine deaminase activityGO:0004794
Substrates: L-threonine
Products: 2-oxobutanoate ammonium
Cofactors: pyridoxal 5'-phosphate

Supplies 2-oxobutanoate for the isoleucine branch. KT2440 has two full-length IlvA-family proteins with the same reviewed pathway assignment; their relative physiological contributions remain unresolved.

Part 2: acetohydroxy-acid formation
Acetohydroxy-acid synthase complexProtein ComplexilvIH_step

IlvI is the catalytic large subunit and IlvH is the non-catalytic regulatory small subunit. The complex accepts either pyruvate plus pyruvate or pyruvate plus 2-oxobutanoate.

acetolactate synthase complexGO:0005948

Annotons

IlvI acetohydroxy-acid synthase catalytic subunit
ilvI_activity
Participant: Family: biosynthetic acetohydroxy-acid synthase large subunit
Family:
biosynthetic acetohydroxy-acid synthase large subunitNCBIfam:TIGR00118
Representative Members: PSEPK IlvIUniProtKB:Q88DY8
Required Function:
acetolactate synthase activityGO:0003984

Function

acetolactate synthase activityGO:0003984
Substrates: pyruvate pyruvate or 2-oxobutanoate
Products: 2-acetolactate or 2-aceto-2-hydroxybutanoate carbon dioxide
Cofactors: thiamine diphosphate FAD magnesium ion
IlvH acetohydroxy-acid synthase regulatory subunit
ilvH_regulator_activity
Participant: Family: biosynthetic acetohydroxy-acid synthase small subunit
Family:
biosynthetic acetohydroxy-acid synthase small subunitNCBIfam:TIGR00119
Representative Members: PSEPK IlvHUniProtKB:Q88DY9
Required Function:
acetolactate synthase regulator activityGO:1990610

Function

acetolactate synthase regulator activityGO:1990610

Regulatory ACT-domain subunit; it contributes regulation rather than the acetolactate-forming chemistry.

Part 3: acetohydroxy-acid reduction and rearrangement
Acetohydroxy acids to dihydroxy acidsReactionilvC_step

Annotons

IlvC ketol-acid reductoisomerase
ilvC_activity
Participant: Family: type I ketol-acid reductoisomerase family
Family:
type I ketol-acid reductoisomerase familyNCBIfam:TIGR00465
Representative Members: PSEPK IlvCUniProtKB:Q88DZ0
Required Function:
ketol-acid reductoisomerase activityGO:0004455

Function

ketol-acid reductoisomerase activityGO:0004455
Substrates: 2-acetolactate or 2-aceto-2-hydroxybutanoate NADPH
Products: 2,3-dihydroxy-3-isovalerate or 2,3-dihydroxy-3-methylpentanoate NADP+
Cofactors: magnesium ion
Part 4: branched-chain 2-oxoacid formation
Dihydroxy acids to branched-chain 2-oxoacidsReactionilvD_step

Annotons

IlvD dihydroxy-acid dehydratase
ilvD_activity
Participant: Family: biosynthetic dihydroxy-acid dehydratase family
Family:
biosynthetic dihydroxy-acid dehydratase familyNCBIfam:TIGR00110
Representative Members: PSEPK IlvDUniProtKB:Q88CQ2
Required Function:
dihydroxy-acid dehydratase activityGO:0004160

Function

dihydroxy-acid dehydratase activityGO:0004160
Substrates: 2,3-dihydroxy-3-isovalerate or 2,3-dihydroxy-3-methylpentanoate
Products: 2-oxoisovalerate or 3-methyl-2-oxopentanoate water
Cofactors: iron-sulfur cluster magnesium ion
Part 5: leucine-specific carbon-chain extension
2-Oxoisovalerate to 2-oxoisocaproateMetabolic Pathwayleucine_extension

Connections

leuA_step -> leuCD_step Precedes
leuCD_step -> leuB_step Precedes
Part 1: committed leucine-branch condensation
2-Oxoisovalerate to 2-isopropylmalateReactionleuA_step

Annotons

LeuA 2-isopropylmalate synthase
leuA_activity
Participant: Family: LeuA 2-isopropylmalate synthase family
Family:
LeuA 2-isopropylmalate synthase familyPANTHER:PTHR46911:SF1
Representative Members: PSEPK LeuAUniProtKB:Q88P28
Required Function:
2-isopropylmalate synthase activityGO:0003852

Function

2-isopropylmalate synthase activityGO:0003852
Substrates: 2-oxoisovalerate acetyl-CoA water
Products: 2-isopropylmalate coenzyme A
Part 2: isopropylmalate isomerization
2-Isopropylmalate to 3-isopropylmalateProtein ComplexleuCD_step

The LeuC-LeuD heteromer performs dehydration and rehydration to move the hydroxyl group from 2-isopropylmalate to 3-isopropylmalate.

3-isopropylmalate dehydratase complexGO:0009316

Annotons

LeuC 3-isopropylmalate dehydratase large subunit
leuC_activity
Participant: Family: 3-isopropylmalate dehydratase large subunit family
Family:
3-isopropylmalate dehydratase large subunit familyNCBIfam:TIGR00170
Representative Members: PSEPK LeuCUniProtKB:Q88LE8
Required Function:
3-isopropylmalate dehydratase activityGO:0003861

Function

3-isopropylmalate dehydratase activityGO:0003861
LeuD 3-isopropylmalate dehydratase small subunit
leuD_activity
Participant: Family: 3-isopropylmalate dehydratase small subunit family
Family:
3-isopropylmalate dehydratase small subunit familyNCBIfam:TIGR00171
Representative Members: PSEPK LeuDUniProtKB:Q88LE7
Required Function:
3-isopropylmalate dehydratase activityGO:0003861

Function

3-isopropylmalate dehydratase activityGO:0003861
Part 3: leucine-branch 2-oxoacid formation
3-Isopropylmalate to 2-oxoisocaproateReactionleuB_step

Annotons

LeuB 3-isopropylmalate dehydrogenase
leuB_activity
Participant: Family: 3-isopropylmalate dehydrogenase family
Family:
3-isopropylmalate dehydrogenase familyNCBIfam:TIGR00169
Representative Members: PSEPK LeuBUniProtKB:Q88LE5
Required Function:
3-isopropylmalate dehydrogenase activityGO:0003862

Function

3-isopropylmalate dehydrogenase activityGO:0003862
Substrates: 3-isopropylmalate NAD+
Products: 2-oxoisocaproate carbon dioxide NADH
Part 6: terminal transamination of all three branches
Branched-chain 2-oxoacids to L-valine, L-leucine, and L-isoleucineReactionilvE_step

Annotons

IlvE branched-chain amino-acid aminotransferase
ilvE_activity
Participant: Family: IlvE branched-chain amino-acid aminotransferase family
Family:
IlvE branched-chain amino-acid aminotransferase familyNCBIfam:TIGR01123
Representative Members: PSEPK IlvEUniProtKB:Q88H54
Required Function:
branched-chain-amino-acid:2-oxoglutarate transaminase activityGO:0004084

Function

branched-chain-amino-acid:2-oxoglutarate transaminase activityGO:0004084
Substrates: 2-oxoisovalerate, 2-oxoisocaproate, or 3-methyl-2-oxopentanoate L-glutamate
Products: L-valine, L-leucine, or L-isoleucine 2-oxoglutarate
Cofactors: pyridoxal 5'-phosphate

A shared reversible enzyme supplies the terminal transamination for the valine, leucine, and isoleucine products.