Ehrlich pathway (amino acid catabolism to fusel alcohols and fusel acids)

Catabolic route by which yeasts and other fungi degrade the branched-chain amino acids (leucine, isoleucine, valine), the aromatic amino acids (phenylalanine, tyrosine, tryptophan) and methionine when these are used as nitrogen sources. Only the amino group is retained by the cell; the carbon skeleton is excreted. The pathway has three steps. A pyridoxal-phosphate aminotransferase first transfers the amino group to an acceptor 2-oxo acid (2-oxoglutarate for the branched-chain aminotransferases; pyruvate or phenylpyruvate for the inducible aromatic aminotransferase), giving the corresponding 2-oxo acid. A thiamine-diphosphate-dependent 2-oxo-acid decarboxylase then irreversibly converts the 2-oxo acid to an aldehyde with one carbon fewer; this is the first step specific to the pathway. Finally, depending on the redox state of the cell, the aldehyde is reduced by NADH alcohol dehydrogenases to a fusel alcohol (isoamyl alcohol, 2-methylbutanol, isobutanol, 2-phenylethanol, tyrosol, tryptophol) or oxidized by aldehyde dehydrogenases to a fusel acid. All three steps are carried out by sets of overlapping isozymes whose use depends on the amino acid, the carbon source and the growth stage. In budding yeast the aminotransferase and decarboxylase of the aromatic branch are co-induced by aromatic amino acids. Oxidative degradation of the 2-oxo acids by the mitochondrial branched-chain 2-oxo acid dehydrogenase complex, the catabolic route that dominates in animals, is outside this module.

MODULE:ehrlich_pathwayDRAFTCONCRETEMetabolic Pathwaymodules/ehrlich_pathway.yaml
branched-chain amino acid catabolic processGO:0009083 aromatic amino acid catabolic processGO:0009074
GO:0009083
branched-chain amino acid catabolic process
Module-level process concept for the branched-chain arm (leucine, isoleucine and valine catabolism).
GO:0009074
aromatic amino acid catabolic process
Module-level process concept for the aromatic arm (phenylalanine, tyrosine and tryptophan catabolism).
GO:0000955
obsolete amino acid catabolic process via Ehrlich pathway
GO formerly had dedicated Ehrlich pathway process terms (GO:0000947 to GO:0000955); all are now obsolete, so the module uses the amino-acid-specific catabolic process terms instead.
YeastPathways:PWY3O-4109
isoleucine degradation (S. cerevisiae, SGD YeastPathways)
YeastCyc lists BAT1/BAT2 transamination, decarboxylation by PDC1, PDC5, PDC6, ARO10 and THI3, and reduction by ADH1-5 and SFA1. THI3 was not retained as a catalyst.
YeastPathways:PWY3O-4112
leucine degradation (S. cerevisiae, SGD YeastPathways)
YeastCyc lists BAT1/BAT2 transamination, decarboxylation of 4-methyl-2-oxopentanoate by ARO10 and THI3, and reduction by ADH1-5 and SFA1. THI3 was not retained; PDC1/5/6 were added because they decarboxylate 4-methyl-2-oxopentanoate.
YeastPathways:PWY3O-4105
valine degradation (S. cerevisiae, SGD YeastPathways)
YeastCyc lists BAT1/BAT2 transamination, decarboxylation of 3-methyl-2-oxobutanoate by PDC1/5/6, and reduction by ADH1-5 and SFA1. All were retained; ARO10 was added as a secondary branched-chain decarboxylase.
YeastPathways:PWY3O-4115
phenylalanine degradation (S. cerevisiae, SGD YeastPathways)
YeastCyc lists phenylalanine transamination by ARO8 and HIS5 (with 2-oxoglutarate) and by ARO9 (with pyruvate), phenylpyruvate decarboxylation by ARO10 and PDC1/5/6, and reduction by ADH1-5 and SFA1. HIS5 was not retained.
YeastPathways:PWY3O-4108
L-tyrosine degradation III (S. cerevisiae, SGD YeastPathways)
YeastCyc lists tyrosine transamination by ARO8 and ARO9 and reduction by ADH1-5, but gives no gene for 4-hydroxyphenylpyruvate decarboxylation (4.1.1.80-RXN). ARO10 was added for that step.
YeastPathways:PWY3O-214
tryptophan degradation (S. cerevisiae, SGD YeastPathways)
YeastCyc lists tryptophan transamination by ARO8 (2-oxoglutarate) and ARO9 (phenylpyruvate), indolepyruvate decarboxylation by ARO10 and PDC1/5/6, and reduction by ADH1-5 and SFA1. All were retained.
PMID:18281432
The Ehrlich pathway for fusel alcohol production: a century of research on Saccharomyces cerevisiae metabolism.
Review of the Ehrlich pathway: transamination, decarboxylation and then reduction or oxidation of the aldehyde, with the yeast isozymes for each step.
PMID:12902239
Identification and characterization of phenylpyruvate decarboxylase genes in Saccharomyces cerevisiae.
Defines the three-step pathway with its oxidative alternative and identifies ARO10 as the physiologically relevant phenylpyruvate decarboxylase; THI3 is not itself an active decarboxylase.
Catabolism of amino acids via the Ehrlich pathway involves transamination to the corresponding alpha-keto acids, followed by decarboxylation to an aldehyde and then reduction to an alcohol. Alternatively, the aldehyde may be oxidized to an acid.
PMID:12499363
The catabolism of amino acids to long chain and complex alcohols in Saccharomyces cerevisiae.
Phenylpyruvate and indolepyruvate are decarboxylated by Pdc1, Pdc5, Pdc6 or Aro10, and the final reduction can be done by any of Adh1-Adh5 or Sfa1.
the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.)
PMID:22904058
Substrate specificity of thiamine pyrophosphate-dependent 2-oxo-acid decarboxylases in Saccharomyces cerevisiae.
Systematic comparison of the five candidate 2-oxo-acid decarboxylases; Thi3 has no activity, Aro10 has the highest affinity for phenylpyruvate and branched-chain 2-oxo acids.
No decarboxylation activity was found for Thi3 with any of the substrates tested. Only Aro10 and Pdc5 catalyzed the decarboxylation of the aromatic substrate phenylpyruvate, with Aro10 showing superior kinetic properties.
PMID:15933030
Physiological characterization of the ARO10-dependent, broad-substrate-specificity 2-oxo acid decarboxylase activity of Saccharomyces cerevisiae.
ARO10 is the only decarboxylase gene induced by phenylalanine, leucine or methionine as nitrogen source and confers broad-substrate 2-oxo-acid decarboxylase activity.
only ARO10 was transcriptionally up-regulated when phenylalanine, leucine, or methionine was used as a nitrogen source compared to growth on ammonia, proline, and asparagine.
PMID:21501384
Characterization of a thiamin diphosphate-dependent phenylpyruvate decarboxylase from Saccharomyces cerevisiae.
Purified Aro10 is an efficient aromatic 2-keto-acid decarboxylase; its in vitro substrate spectrum argues against a major role with branched-chain 2-oxo acids (contrast PMID:22904058).
The enzyme is shown to be an efficient aromatic 2-keto acid decarboxylase, consistent with it playing a major in vivo role in phenylalanine, tryptophan and possibly also tyrosine catabolism.
PMID:9546164
Pyruvate decarboxylase catalyzes decarboxylation of branched-chain 2-oxo acids but is not essential for fusel alcohol production by Saccharomyces cerevisiae.
Pdc1 and Pdc5 decarboxylate branched-chain 2-oxo acids, but a Pdc-negative strain still forms branched-chain fusel alcohols.
Experiments with cell extracts from S. cerevisiae mutants expressing a single PDC gene demonstrated that both PDC1- and PDC5-encoded isoenzymes can decarboxylate branched-chain 2-oxo acids.
PMID:9748245
An investigation of the metabolism of valine to isobutyl alcohol in Saccharomyces cerevisiae.
Valine-derived 2-oxoisovalerate is decarboxylated by pyruvate decarboxylase; the branched-chain 2-oxo acid dehydrogenase route is not needed for isobutyl alcohol formation.
any single isozyme of pyruvate decarboxylase is sufficient for the formation of isobutyl alcohol from valine.
PMID:9341119
A 13C nuclear magnetic resonance investigation of the metabolism of leucine to isoamyl alcohol in Saccharomyces cerevisiae.
Leucine-derived 2-oxoisocaproate is converted to isoamyl alcohol by decarboxylation rather than through the branched-chain 2-oxo acid dehydrogenase. The paper attributed the decarboxylation mainly to YDL080c (THI3), which was later shown not to be an active decarboxylase (PMID:22904058).
PMID:10753893
An investigation of the metabolism of isoleucine to active Amyl alcohol in Saccharomyces cerevisiae.
Any one of the Pdc1/Pdc5/Pdc6/YDL080c/YDR380w (ARO10) decarboxylase family is sufficient for isoleucine catabolism to 2-methylbutanol.
Apparently, any one of this family of decarboxylases is sufficient to allow the catabolism of isoleucine to active amyl alcohol.
PMID:8702755
Two yeast homologs of ECA39, a target for c-Myc regulation, code for cytosolic and mitochondrial branched-chain amino acid aminotransferases.
BAT1 (ECA39) and BAT2 (ECA40) encode the mitochondrial and cytosolic branched-chain aminotransferases; BAT2 is expressed mainly in stationary phase.
ECA39 is highly expressed during log phase and is down-regulated during the stationary phase of growth, while ECA40 shows an inverse pattern of gene expression.
PMID:8798704
Mitochondrial and cytosolic branched-chain amino acid transaminases from yeast, homologs of the myc oncogene-regulated Eca39 protein.
Bat1 is in the mitochondrial matrix and Bat2 in the cytosol.
A highly homologous protein, Bat2p, of 376 amino acid residues was found in the cytosol.
PMID:10207060
Transcriptional induction by aromatic amino acids in Saccharomyces cerevisiae.
ARO9 catalyses the first step of aromatic amino acid catabolism and is co-induced with ARO10 by the Aro80 activator.
Aromatic aminotransferase II, product of the ARO9 gene, catalyzes the first step of tryptophan, phenylalanine, and tyrosine catabolism in Saccharomyces cerevisiae.
PMID:9491083
Characterisation of Saccharomyces cerevisiae ARO8 and ARO9 genes encoding aromatic aminotransferases I and II reveals a new aminotransferase subfamily.
ARO8 and ARO9 encode aromatic aminotransferases I and II; ARO9 is induced by aromatic amino acids.
ARO9 expression is induced when aromatic amino acids are present in the growth medium
PMID:6763508
Tryptophan degradation in Saccharomyces cerevisiae: characterization of two aromatic aminotransferases.
Biochemical characterization of aromatic aminotransferases I and II (cited by YeastPathways for amino-acceptor specificity).
PMID:23836015
Metabolic engineering of Saccharomyces cerevisiae for the production of 2-phenylethanol via Ehrlich pathway.
Ald3 is mainly responsible for oxidizing phenylacetaldehyde, the oxidative (fusel acid) branch competing with 2-phenylethanol formation.
We demonstrated that Ald3 is mainly responsible for phenylacetaldehyde oxidation, competing with 2-PE production.
10Nodes
3Parts
3Variant Sets
6Variants
13Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:ehrlich_pathway 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.

  • transamination_step → decarboxylation_step [NOT_CHECKED]
    The 2-oxo acid made by transamination (for example phenylpyruvate, 4-methyl-2-oxopentanoate) is the decarboxylase substrate; no CoA intermediate is involved.
  • decarboxylation_step → aldehyde_fate_step [NOT_CHECKED]
    The fusel aldehyde made by decarboxylation is reduced by ADH or oxidized by ALD; no CoA intermediate is involved.

Function consistency and core coverage

19 gene-function check(s) reflected in core functions · 0 conflict(s) · 10 evidence or coverage gap(s) (33 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
bat2_catabolic_transaminase BAT2 (Saccharomyces cerevisiae)
UniProtKB:P47176
Family Representative 		branched-chain-amino-acid:2-oxoglutarate transaminase activity
GO:0004084 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bat1_mitochondrial_transaminase BAT1 (Saccharomyces cerevisiae)
UniProtKB:P38891
Family Representative 		branched-chain-amino-acid:2-oxoglutarate transaminase activity
GO:0004084 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aro9_phe_transaminase ARO9 (Saccharomyces cerevisiae)
UniProtKB:P38840
Family Representative 		L-phenylalanine:pyruvate transaminase activity
GO:0047312 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aro9_tyr_transaminase ARO9 (Saccharomyces cerevisiae)
UniProtKB:P38840
Family Representative 		L-tyrosine:pyruvate transaminase activity
GO:0080098 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aro9_trp_transaminase ARO9 (Saccharomyces cerevisiae)
UniProtKB:P38840
Family Representative 		L-tryptophan:phenylpyruvate transaminase activity
GO:0047299 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aro8_aromatic_transaminase ARO8 (Saccharomyces cerevisiae)
UniProtKB:P53090
Family Representative 		aromatic-amino-acid:2-oxoglutarate transaminase activity
GO:0008793 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aro10_phenylpyruvate_decarboxylase ARO10 (Saccharomyces cerevisiae)
UniProtKB:Q06408
Family Representative 		phenylpyruvate decarboxylase activity
GO:0050177 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aro10_hydroxyphenylpyruvate_decarboxylase ARO10 (Saccharomyces cerevisiae)
UniProtKB:Q06408
Family Representative 		4-hydroxyphenylpyruvate decarboxylase activity
GO:0050546 		Annotation Supported
A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
aro10_indolepyruvate_decarboxylase ARO10 (Saccharomyces cerevisiae)
UniProtKB:Q06408
Family Representative 		indolepyruvate decarboxylase activity
GO:0047434 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aro10_branched_chain_decarboxylase ARO10 (Saccharomyces cerevisiae)
UniProtKB:Q06408
Family Representative 		branched-chain-2-oxoacid decarboxylase activity
GO:0047433 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdc_branched_chain_decarboxylase PDC1 (Saccharomyces cerevisiae)
UniProtKB:P06169
Family Representative 		branched-chain-2-oxoacid decarboxylase activity
GO:0047433 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdc_branched_chain_decarboxylase PDC5 (Saccharomyces cerevisiae)
UniProtKB:P16467
Family Representative 		branched-chain-2-oxoacid decarboxylase activity
GO:0047433 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdc_branched_chain_decarboxylase PDC6 (Saccharomyces cerevisiae)
UniProtKB:P26263
Family Representative 		branched-chain-2-oxoacid decarboxylase activity
GO:0047433 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
adh_fusel_alcohol_formation ADH1 (Saccharomyces cerevisiae)
UniProtKB:P00330
Family Representative 		alcohol dehydrogenase (NAD+) activity
GO:0004022 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
adh_fusel_alcohol_formation ADH2 (Saccharomyces cerevisiae)
UniProtKB:P00331
Family Representative 		alcohol dehydrogenase (NAD+) activity
GO:0004022 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
adh_fusel_alcohol_formation ADH3 (Saccharomyces cerevisiae)
UniProtKB:P07246
Family Representative 		alcohol dehydrogenase (NAD+) activity
GO:0004022 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
adh_fusel_alcohol_formation ADH4 (Saccharomyces cerevisiae)
UniProtKB:P10127
Family Representative 		alcohol dehydrogenase (NAD+) activity
GO:0004022 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
adh_fusel_alcohol_formation ADH5 (Saccharomyces cerevisiae)
UniProtKB:P38113
Family Representative 		alcohol dehydrogenase (NAD+) activity
GO:0004022 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
adh_fusel_alcohol_formation SFA1 (Saccharomyces cerevisiae)
UniProtKB:P32771
Family Representative 		alcohol dehydrogenase (NAD+) activity
GO:0004022 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ald_fusel_acid_formation ALD3 (Saccharomyces cerevisiae)
UniProtKB:P54114
Family Representative 		aldehyde dehydrogenase (NAD+) activity
GO:0004029 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bat2_catabolic_transaminase branched-chain amino acid aminotransferase (fold-type IV)
PANTHER:PTHR11825:SF44
Family 		branched-chain-amino-acid:2-oxoglutarate transaminase activity
GO:0004084 		Family Supported
Family review supports GO:0004084 FAMILY_WIDE. The PANTHER subfamily inventory comprises branched-chain aminotransferase, BCAT1 and BCAT2 groups. Rat BCAT2 expression directly produces branched-chain aminotransferase activity with processing of its mitochondrial targeting sequence (PMID:9165094); the human ortholog and reviewed substrate chemistry support the same broad reaction. This supports the reaction across intact members, while the shared class-IV PLP fold alone would not: mitochondrial location, catabolic direction and physiological substrate flux differ among lineages.
bat1_mitochondrial_transaminase branched-chain amino acid aminotransferase (fold-type IV)
PANTHER:PTHR11825:SF44
Family 		branched-chain-amino-acid:2-oxoglutarate transaminase activity
GO:0004084 		Family Supported
Family review supports GO:0004084 FAMILY_WIDE. The PANTHER subfamily inventory comprises branched-chain aminotransferase, BCAT1 and BCAT2 groups. Rat BCAT2 expression directly produces branched-chain aminotransferase activity with processing of its mitochondrial targeting sequence (PMID:9165094); the human ortholog and reviewed substrate chemistry support the same broad reaction. This supports the reaction across intact members, while the shared class-IV PLP fold alone would not: mitochondrial location, catabolic direction and physiological substrate flux differ among lineages.
aro9_phe_transaminase aromatic/aminoadipate aminotransferase subfamily (class I)
PANTHER:PTHR42790:SF2
Family 		L-phenylalanine:pyruvate transaminase activity
GO:0047312 		Family Scope Restricted
GO:0008483 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Safe for the enzyme subfamilies (aromatic aminotransferases SF1, SF2, SF21 and SF23, AvtA SF4) and for SF19, whose AADAT, LysN and archaeal members are aminotransferases. Even within SF19 the PtsJ and NorG regulators should not be assumed to have the activity. Not safe for the MocR regulator subfamilies (SF6, SF7, SF8, SF9, SF17, SF20, SF22). Both yeast gene reviews accept the IBA.
aro9_tyr_transaminase aromatic/aminoadipate aminotransferase subfamily (class I)
PANTHER:PTHR42790:SF2
Family 		L-tyrosine:pyruvate transaminase activity
GO:0080098 		Family Scope Restricted
GO:0008483 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Safe for the enzyme subfamilies (aromatic aminotransferases SF1, SF2, SF21 and SF23, AvtA SF4) and for SF19, whose AADAT, LysN and archaeal members are aminotransferases. Even within SF19 the PtsJ and NorG regulators should not be assumed to have the activity. Not safe for the MocR regulator subfamilies (SF6, SF7, SF8, SF9, SF17, SF20, SF22). Both yeast gene reviews accept the IBA.
aro9_trp_transaminase aromatic/aminoadipate aminotransferase subfamily (class I)
PANTHER:PTHR42790:SF2
Family 		L-tryptophan:phenylpyruvate transaminase activity
GO:0047299 		Family Scope Restricted
GO:0008483 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Safe for the enzyme subfamilies (aromatic aminotransferases SF1, SF2, SF21 and SF23, AvtA SF4) and for SF19, whose AADAT, LysN and archaeal members are aminotransferases. Even within SF19 the PtsJ and NorG regulators should not be assumed to have the activity. Not safe for the MocR regulator subfamilies (SF6, SF7, SF8, SF9, SF17, SF20, SF22). Both yeast gene reviews accept the IBA.
aro8_aromatic_transaminase aromatic/aminoadipate aminotransferase subfamily (class I)
PANTHER:PTHR42790:SF21
Family 		aromatic-amino-acid:2-oxoglutarate transaminase activity
GO:0008793 		Family Scope Restricted
GO:0008483 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Safe for the enzyme subfamilies (aromatic aminotransferases SF1, SF2, SF21 and SF23, AvtA SF4) and for SF19, whose AADAT, LysN and archaeal members are aminotransferases. Even within SF19 the PtsJ and NorG regulators should not be assumed to have the activity. Not safe for the MocR regulator subfamilies (SF6, SF7, SF8, SF9, SF17, SF20, SF22). Both yeast gene reviews accept the IBA.
aro10_phenylpyruvate_decarboxylase transaminated amino acid decarboxylase (ARO10 subfamily)
PANTHER:PTHR43452:SF3
Family 		phenylpyruvate decarboxylase activity
GO:0050177 		Family Function Unreviewed
Family review leaves GO:0050177 UNRESOLVED. ARO10 (SF3) is the physiologically relevant phenylpyruvate decarboxylase. Among the SF30 PDCs only PDC5 decarboxylates phenylpyruvate, so the term is a gene-level property there, not a subfamily-level one.
aro10_hydroxyphenylpyruvate_decarboxylase transaminated amino acid decarboxylase (ARO10 subfamily)
PANTHER:PTHR43452:SF3
Family 		4-hydroxyphenylpyruvate decarboxylase activity
GO:0050546 		Family Function Unreviewed
Family review leaves GO:0050546 UNRESOLVED. The Ehrlich pathway module assigns this activity to ARO10 (SF3) for the tyrosine branch, but the ARO10 gene review does not include it among its core functions, and the cited kinetic study only calls a tyrosine role possible. Plausible from the aromatic substrate preference, but not established here.
aro10_indolepyruvate_decarboxylase transaminated amino acid decarboxylase (ARO10 subfamily)
PANTHER:PTHR43452:SF3
Family 		indolepyruvate decarboxylase activity
GO:0047434 		Family Function Unreviewed
Family review leaves GO:0047434 UNRESOLVED. ARO10 (SF3) is an efficient aromatic 2-keto acid decarboxylase with a role in tryptophan catabolism. Bacterial IpdC enzymes in SF30 are named indolepyruvate decarboxylases, but SF30 as a whole is not assigned this term because it also contains the yeast pyruvate decarboxylases and THI3. The PDC gene reviews retain the term as a minor, redundant activity inferred from Dickinson et al. genetics, so no subfamily-level scope is safe.
aro10_branched_chain_decarboxylase transaminated amino acid decarboxylase (ARO10 subfamily)
PANTHER:PTHR43452:SF3
Family 		branched-chain-2-oxoacid decarboxylase activity
GO:0047433 		Family Supported
Family review supports GO:0047433 for PANTHER:PTHR43452:SF3. Shown for the S. cerevisiae PDC1, PDC5, PDC6 (SF30) and ARO10 (SF3) enzymes, which all decarboxylate branched-chain 2-oxo acids with different kinetics; ARO10 is the high-affinity enzyme. Used by the Ehrlich pathway module for both SF30 and SF3. Not established for the plant or SF1 enzymes, and THI3 (SF30) is inactive.
pdc_branched_chain_decarboxylase pyruvate decarboxylase isozymes
PANTHER:PTHR43452:SF30
Family 		branched-chain-2-oxoacid decarboxylase activity
GO:0047433 		Family Supported
Family review supports GO:0047433 for PANTHER:PTHR43452:SF30. Shown for the S. cerevisiae PDC1, PDC5, PDC6 (SF30) and ARO10 (SF3) enzymes, which all decarboxylate branched-chain 2-oxo acids with different kinetics; ARO10 is the high-affinity enzyme. Used by the Ehrlich pathway module for both SF30 and SF3. Not established for the plant or SF1 enzymes, and THI3 (SF30) is inactive.
adh_fusel_alcohol_formation alcohol dehydrogenases (zinc-dependent ADH1/2/3/5 and SFA1; iron-type ADH4)
Family 		alcohol dehydrogenase (NAD+) activity
GO:0004022 		Family Id Missing
The family has no identifier linking it to a curated family review.
ald_fusel_acid_formation cytosolic NAD(P)+-dependent aldehyde dehydrogenase (ALD2/ALD3 group)
Family 		aldehyde dehydrogenase (NAD+) activity
GO:0004029 		Family Id Missing
The family has no identifier linking it to a curated family review.

Gene-review completeness (15/15 grounded genes reviewed)

9 complete review(s) · 15 with deep research · 0 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
ADH1 P00330 ✓ 58/60 ✓
ADH2 P00331 ✓ ✓ ✓
ADH3 P07246 ✓ ✓ ✓
ADH4 P10127 ✓ 35/43 ✓
ADH5 P38113 ✓ ✓ ✓
ALD3 P54114 ✓ ✓ ✓
ARO10 Q06408 ✓ ✓ ✓
ARO8 P53090 ✓ ✓ ✓
ARO9 P38840 ✓ ✓ ✓
BAT1 P38891 ✓ ✓ ✓
BAT2 P47176 ✓ ✓ ✓
PDC1 P06169 ✓ 54/59 ✓
PDC5 P16467 ✓ 58/60 ✓
PDC6 P26263 ✓ 47/52 ✓
SFA1 P32771 ✓ 48/50 ✓

Details

Context
fungiNCBITaxon:4751
Ehrlich pathway (amino acid catabolism to fusel alcohols and fusel acids)Metabolic Pathwayehrlich_pathway
branched-chain amino acid catabolic processGO:0009083 aromatic amino acid catabolic processGO:0009074
Context
fungiNCBITaxon:4751

NEW module (YeastPathways crosswalk, 2026-10) generalising six YeastCyc frames (PWY3O-4109 isoleucine, PWY3O-4112 leucine, PWY3O-4105 valine, PWY3O-4115 phenylalanine, PWY3O-4108 tyrosine, PWY3O-214 tryptophan degradation) into one three-step pathway with the substrate class and enzyme isoform as variant axes. Methionine is degraded by the same enzymes to methionol but has no YeastCyc frame in this group and is not modelled as a separate variant. GO's dedicated Ehrlich pathway process terms are all obsolete, so concepts use GO:0009083 and GO:0009074 and leaves use the amino-acid-specific catabolic process terms. Gene corrections to YeastCyc: (1) THI3 is removed as a catalyst. It has no detectable decarboxylase activity (PMID:22904058) and acts as a regulator of thiamine metabolism; its early assignment as the main leucine decarboxylase (PMID:9341119) is superseded. (2) ARO10 is added to the valine frame and to the tyrosine frame, which lists no gene for 4.1.1.80-RXN. (3) PDC1/5/6 are added to the leucine frame, because Pdc isozymes decarboxylate 4-methyl-2-oxopentanoate (PMID:22904058, PMID:9546164). (4) HIS5 (histidinol-phosphate aminotransferase) is removed from phenylalanine transamination (RXN-10814); aro8 aro9 mutants show that Aro8/Aro9 carry aromatic transamination. (5) The oxidative fusel-acid branch (ALD3) is added; YeastCyc only models reduction. (6) BAT1 is mitochondrial, not cytosolic, and is kept as a minor, mainly biosynthetic contributor; BAT2 is the catabolic transaminase. GO-CAM disagreements (SGD models): BAT1/BAT2 are typed with the isoleucine-specific GO:0052656 in the leucine and valine models instead of GO:0004084; ARO9 is typed with the 2-oxoglutarate term GO:0008793 for a pyruvate-dependent reaction although Aro9 does not use 2-oxoglutarate (this module uses GO:0047312, GO:0080098 and GO:0047299); ARO8 and ARO9 tyrosine transamination are typed only as GO:0003674; ARO10 is typed with phenylpyruvate decarboxylase for the leucine 2-oxo acid; the tyrosine model gives PDC1/5/6 but not ARO10 for 4-hydroxyphenylpyruvate decarboxylation; and BAT1 and ADH3 are placed in the cytosol. The SGD models have no causal links. Excluded from the module: the mitochondrial branched-chain 2-oxo acid dehydrogenase route (not needed for fusel alcohol formation, PMID:9341119, PMID:9748245); amino acid uptake by Gap1 and Wap1/Agp1; the Aro80 transcriptional activator; and CHA1, the catabolic serine/threonine dehydratase, which is the catabolic counterpart of ILV1 rather than an Ehrlich enzyme. BAT1 and ARO8 are also members of the branched_chain_amino_acid_biosynthesis and phenylalanine_tyrosine_biosynthesis modules. Pyruvate decarboxylases and ADH1 are shared with alcoholic fermentation.

Connections

Part 1: transamination of the amino acid to its 2-oxo acid
amino acid + acceptor 2-oxo acid to 2-oxo acid + amino acidReactiontransamination_step
Variant set: Branched-chain versus aromatic aminotransferases by substrate class (One Or More)

The amino-acid class decides which aminotransferase acts. The reactions are reversible and shared with the final steps of the corresponding biosynthetic pathways; the catabolic isozymes are the ones induced under catabolic conditions (BAT2, ARO9).

Branched-chain amino acid transaminationReactionbcaa_transamination

Annotons

Cytosolic branched-chain aminotransferase (catabolic isozyme)
bat2_catabolic_transaminase
Participant: Family: branched-chain amino acid aminotransferase (fold-type IV)
Family:
branched-chain amino acid aminotransferase (fold-type IV)PANTHER:PTHR11825:SF44
Representative Members: BAT2 (Saccharomyces cerevisiae)UniProtKB:P47176

Function

branched-chain-amino-acid:2-oxoglutarate transaminase activityGO:0004084
Substrates: L-leucine, L-isoleucine or L-valine 2-oxoglutarate
Products: 4-methyl-2-oxopentanoate, (S)-3-methyl-2-oxopentanoate or 3-methyl-2-oxobutanoate L-glutamate

Processes

L-leucine catabolic processGO:0006552 L-isoleucine catabolic processGO:0006550 L-valine catabolic processGO:0006574

Locations

cytosolGO:0005829

Removes the amino group of the branched-chain amino acids, transferring it to 2-oxoglutarate. BAT2 is the main catabolic isozyme; it also contributes redundantly to the last biosynthetic step.

file:yeast/BAT2/BAT2-ai-review.yaml
The BAT2 review makes GO:0004084 a core function in leucine, isoleucine and valine catabolism, in the cytosol.
Mitochondrial branched-chain aminotransferase (minor catabolic contribution)
bat1_mitochondrial_transaminase
Participant: Family: branched-chain amino acid aminotransferase (fold-type IV)
Family:
branched-chain amino acid aminotransferase (fold-type IV)PANTHER:PTHR11825:SF44
Representative Members: BAT1 (Saccharomyces cerevisiae)UniProtKB:P38891

Function

branched-chain-amino-acid:2-oxoglutarate transaminase activityGO:0004084

Locations

mitochondrial matrixGO:0005759

Mitochondrial paralog that mainly carries out the last step of branched-chain amino acid biosynthesis. It can transaminate the same substrates, but its expression falls under catabolic conditions, so its contribution to the Ehrlich pathway is minor. No catabolic process is asserted for it here.

file:yeast/BAT1/BAT1-ai-review.yaml
The BAT1 review makes GO:0004084 a core function in branched-chain amino acid biosynthesis in the mitochondrial matrix and attributes most catabolic transamination to BAT2.
Aromatic amino acid transaminationReactionaromatic_transamination

Annotons

Inducible aromatic aminotransferase II (phenylalanine, pyruvate acceptor)
aro9_phe_transaminase
Participant: Family: aromatic/aminoadipate aminotransferase subfamily (class I)
Family:
aromatic/aminoadipate aminotransferase subfamily (class I)PANTHER:PTHR42790:SF2
Representative Members: ARO9 (Saccharomyces cerevisiae)UniProtKB:P38840

Function

L-phenylalanine:pyruvate transaminase activityGO:0047312
Substrates: L-phenylalanine pyruvate
Products: phenylpyruvate L-alanine

Processes

L-phenylalanine catabolic processGO:0006559

Locations

cytosolGO:0005829

First step of phenylalanine catabolism. ARO9 uses pyruvate or phenylpyruvate, not 2-oxoglutarate, as amino acceptor.

file:yeast/ARO9/ARO9-ai-review.yaml
The ARO9 review makes GO:0047312 a core function in phenylalanine catabolism, in the cytosol.
Inducible aromatic aminotransferase II (tyrosine, pyruvate acceptor)
aro9_tyr_transaminase
Participant: Family: aromatic/aminoadipate aminotransferase subfamily (class I)
Family:
aromatic/aminoadipate aminotransferase subfamily (class I)PANTHER:PTHR42790:SF2
Representative Members: ARO9 (Saccharomyces cerevisiae)UniProtKB:P38840

Function

L-tyrosine:pyruvate transaminase activityGO:0080098
Substrates: L-tyrosine pyruvate
Products: 3-(4-hydroxyphenyl)pyruvate L-alanine

Processes

L-tyrosine catabolic processGO:0006572

Locations

cytosolGO:0005829

First step of tyrosine catabolism to tyrosol.

file:yeast/ARO9/ARO9-ai-review.yaml
The ARO9 review makes GO:0080098 a core function in tyrosine catabolism.
Inducible aromatic aminotransferase II (tryptophan, phenylpyruvate acceptor)
aro9_trp_transaminase
Participant: Family: aromatic/aminoadipate aminotransferase subfamily (class I)
Family:
aromatic/aminoadipate aminotransferase subfamily (class I)PANTHER:PTHR42790:SF2
Representative Members: ARO9 (Saccharomyces cerevisiae)UniProtKB:P38840

Function

L-tryptophan:phenylpyruvate transaminase activityGO:0047299
Substrates: L-tryptophan phenylpyruvate
Products: (indol-3-yl)pyruvate L-phenylalanine

Processes

L-tryptophan catabolic processGO:0006569

Locations

cytosolGO:0005829

First step of tryptophan catabolism to tryptophol; phenylpyruvate serves as amino acceptor.

file:yeast/ARO9/ARO9-ai-review.yaml
The ARO9 review makes GO:0047299 a core function in tryptophan catabolism.
Constitutive aromatic aminotransferase I (2-oxoglutarate acceptor)
aro8_aromatic_transaminase
Participant: Family: aromatic/aminoadipate aminotransferase subfamily (class I)
Family:
aromatic/aminoadipate aminotransferase subfamily (class I)PANTHER:PTHR42790:SF21
Representative Members: ARO8 (Saccharomyces cerevisiae)UniProtKB:P53090

Function

aromatic-amino-acid:2-oxoglutarate transaminase activityGO:0008793

Locations

cytosolGO:0005829

Broad-specificity, constitutive aromatic aminotransferase that can transaminate phenylalanine, tyrosine and tryptophan with 2-oxoglutarate. Its main role is in biosynthesis, so no catabolic process is asserted for it here.

file:yeast/ARO8/ARO8-ai-review.yaml
The ARO8 review makes GO:0008793 a core function in phenylalanine and tyrosine biosynthesis.
Part 2: thiamine-diphosphate-dependent decarboxylation of the 2-oxo acid (first pathway-specific step)
2-oxo acid to aldehyde + CO2Reactiondecarboxylation_step
Variant set: Broad-specificity 2-oxo-acid decarboxylase versus pyruvate decarboxylases by enzyme (substrate preference) (One Or More)

The two enzyme classes overlap. ARO10 dominates for the aromatic 2-oxo acids and is the high-affinity enzyme induced on catabolic nitrogen sources; the pyruvate decarboxylases account for most decarboxylation of 3-methyl-2-oxobutanoate (valine) and contribute to the other branched-chain 2-oxo acids. Leucine-derived 4-methyl-2-oxopentanoate is decarboxylated by ARO10 and the PDCs. THI3 (YDL080C), listed by YeastCyc and once proposed as the main leucine decarboxylase, shows no decarboxylase activity and is excluded.

ARO10-type broad-specificity 2-oxo-acid decarboxylaseReactionaro10_decarboxylase

Annotons

ARO10 phenylpyruvate decarboxylase
aro10_phenylpyruvate_decarboxylase
Participant: Family: transaminated amino acid decarboxylase (ARO10 subfamily)
Family:
transaminated amino acid decarboxylase (ARO10 subfamily)PANTHER:PTHR43452:SF3
Representative Members: ARO10 (Saccharomyces cerevisiae)UniProtKB:Q06408

Function

phenylpyruvate decarboxylase activityGO:0050177
Substrates: phenylpyruvate
Products: phenylacetaldehyde CO2

Processes

L-phenylalanine catabolic processGO:0006559

Locations

cytosolGO:0005829

Physiologically dominant phenylpyruvate decarboxylase; the enzyme YeastCyc omits from several frames.

PMID:12902239
ARO10 is the physiologically relevant phenylpyruvate decarboxylase.
Aro10p is the physiologically relevant phenylpyruvate decarboxylase in wild-type cells.
ARO10 4-hydroxyphenylpyruvate decarboxylase
aro10_hydroxyphenylpyruvate_decarboxylase
Participant: Family: transaminated amino acid decarboxylase (ARO10 subfamily)
Family:
transaminated amino acid decarboxylase (ARO10 subfamily)PANTHER:PTHR43452:SF3
Representative Members: ARO10 (Saccharomyces cerevisiae)UniProtKB:Q06408

Function

4-hydroxyphenylpyruvate decarboxylase activityGO:0050546
Substrates: 3-(4-hydroxyphenyl)pyruvate
Products: (4-hydroxyphenyl)acetaldehyde CO2

Processes

L-tyrosine catabolic processGO:0006572

Locations

cytosolGO:0005829

Tyrosine-branch decarboxylation to (4-hydroxyphenyl)acetaldehyde, the tyrosol precursor. YeastCyc gives no gene for this reaction; ARO10 is added on the basis of in vitro activity (PMID:21501384).

PMID:21501384
Purified Aro10 is an aromatic 2-keto-acid decarboxylase, possibly acting in tyrosine catabolism.
consistent with it playing a major in vivo role in phenylalanine, tryptophan and possibly also tyrosine catabolism.

Tentative assignment. The ARO10 gene review restricts its core functions to the phenylalanine (GO:0050177) and tryptophan (GO:0047434) branches, and the PTHR43452 family review leaves GO:0050546 UNRESOLVED for SF3. The step is retained because tyrosol is a well-known Ehrlich product, but which decarboxylase acts on 4-hydroxyphenylpyruvate in vivo is not established.

ARO10 indolepyruvate decarboxylase
aro10_indolepyruvate_decarboxylase
Participant: Family: transaminated amino acid decarboxylase (ARO10 subfamily)
Family:
transaminated amino acid decarboxylase (ARO10 subfamily)PANTHER:PTHR43452:SF3
Representative Members: ARO10 (Saccharomyces cerevisiae)UniProtKB:Q06408

Function

indolepyruvate decarboxylase activityGO:0047434
Substrates: (indol-3-yl)pyruvate
Products: (indol-3-yl)acetaldehyde CO2

Processes

L-tryptophan catabolic processGO:0006569

Locations

cytosolGO:0005829

Tryptophan-branch decarboxylation to indole-3-acetaldehyde.

ARO10 branched-chain 2-oxo-acid decarboxylase
aro10_branched_chain_decarboxylase
Participant: Family: transaminated amino acid decarboxylase (ARO10 subfamily)
Family:
transaminated amino acid decarboxylase (ARO10 subfamily)PANTHER:PTHR43452:SF3
Representative Members: ARO10 (Saccharomyces cerevisiae)UniProtKB:Q06408

Function

branched-chain-2-oxoacid decarboxylase activityGO:0047433
Substrates: 4-methyl-2-oxopentanoate or (S)-3-methyl-2-oxopentanoate
Products: 3-methylbutanal or 2-methylbutanal CO2

Processes

L-leucine catabolic processGO:0006552 L-isoleucine catabolic processGO:0006550

Locations

cytosolGO:0005829

High-affinity decarboxylation of the leucine- and isoleucine-derived 2-oxo acids during growth on these amino acids as nitrogen source. Its importance relative to the PDCs is disputed (PMID:22904058 versus PMID:21501384).

PMID:22904058
Aro10 decarboxylates branched-chain 2-oxo acids with high affinity.
The high affinity of Aro10 identified it as a key contributor to the production of branched-chain and sulfur-containing fusel alcohols.
Pyruvate decarboxylase isozymes acting on branched-chain and aromatic 2-oxo acidsReactionpdc_decarboxylase

Annotons

Pyruvate decarboxylase (branched-chain 2-oxo acids)
pdc_branched_chain_decarboxylase
Participant: Family: pyruvate decarboxylase isozymes
Family:
pyruvate decarboxylase isozymesPANTHER:PTHR43452:SF30
Representative Members: PDC1 (Saccharomyces cerevisiae)UniProtKB:P06169 PDC5 (Saccharomyces cerevisiae)UniProtKB:P16467 PDC6 (Saccharomyces cerevisiae)UniProtKB:P26263

Function

branched-chain-2-oxoacid decarboxylase activityGO:0047433
Substrates: 3-methyl-2-oxobutanoate, (S)-3-methyl-2-oxopentanoate or 4-methyl-2-oxopentanoate
Products: isobutanal, 2-methylbutanal or 3-methylbutanal CO2

Processes

L-valine catabolic processGO:0006574 L-isoleucine catabolic processGO:0006550 L-leucine catabolic processGO:0006552

Locations

cytosolGO:0005829

Side activity of the glycolytic pyruvate decarboxylases on branched-chain 2-oxo acids. Any single PDC isozyme suffices for isobutanol formation from valine. PDC5 (and weakly the others) also decarboxylates phenylpyruvate and indolepyruvate.

PMID:9748245
Pyruvate decarboxylase is the route for valine-derived 2-oxoisovalerate.
The second route, via pyruvate decarboxylase, is the one that is used because elimination of pyruvate decarboxylase activity in a pdc1 pdc5 pdc6 triple mutant virtually abolished isobutyl alcohol production.
PMID:9546164
Pdc1 and Pdc5 decarboxylate branched-chain 2-oxo acids.
both PDC1- and PDC5-encoded isoenzymes can decarboxylate branched-chain 2-oxo acids.
Part 3: fate of the fusel aldehyde (reduction to fusel alcohol or oxidation to fusel acid)
fusel aldehyde to fusel alcohol or fusel acidReactionaldehyde_fate_step
Variant set: Reductive (fusel alcohol) versus oxidative (fusel acid) branch by redox route (One Or More)

The partition between alcohol and acid depends on the redox state of the cell: reduction predominates during fermentation, oxidation under respiratory conditions.

Reduction to fusel alcohol by alcohol dehydrogenasesReactionreduction_to_fusel_alcohol

Annotons

NADH-dependent alcohol dehydrogenases
adh_fusel_alcohol_formation
Participant: Family: alcohol dehydrogenases (zinc-dependent ADH1/2/3/5 and SFA1; iron-type ADH4)
Family:
alcohol dehydrogenases (zinc-dependent ADH1/2/3/5 and SFA1; iron-type ADH4)
Representative Members: ADH1 (Saccharomyces cerevisiae)UniProtKB:P00330 ADH2 (Saccharomyces cerevisiae)UniProtKB:P00331 ADH3 (Saccharomyces cerevisiae)UniProtKB:P07246 ADH4 (Saccharomyces cerevisiae)UniProtKB:P10127 ADH5 (Saccharomyces cerevisiae)UniProtKB:P38113 SFA1 (Saccharomyces cerevisiae)UniProtKB:P32771

Function

alcohol dehydrogenase (NAD+) activityGO:0004022
Substrates: fusel aldehyde (3-methylbutanal, 2-methylbutanal, isobutanal, phenylacetaldehyde, (4-hydroxyphenyl)acetaldehyde, indole-3-acetaldehyde) NADH
Products: fusel alcohol (isoamyl alcohol, 2-methylbutanol, isobutanol, 2-phenylethanol, tyrosol, tryptophol) NAD+

Any one of ADH1-ADH5 or SFA1 can reduce the fusel aldehydes; the reaction regenerates NAD+. No single enzyme is required. ADH3 acts in mitochondria, the others in the cytosol, so no location is asserted for the role.

PMID:12499363
Any one of Adh1-Adh5 or Sfa1 performs the final reduction.
can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p
Oxidation to fusel acid by aldehyde dehydrogenaseReactionoxidation_to_fusel_acid

Annotons

Cytosolic aldehyde dehydrogenase
ald_fusel_acid_formation
Participant: Family: cytosolic NAD(P)+-dependent aldehyde dehydrogenase (ALD2/ALD3 group)
Family:
cytosolic NAD(P)+-dependent aldehyde dehydrogenase (ALD2/ALD3 group)
Representative Members: ALD3 (Saccharomyces cerevisiae)UniProtKB:P54114

Function

aldehyde dehydrogenase (NAD+) activityGO:0004029
Substrates: fusel aldehyde (for example phenylacetaldehyde) NAD+
Products: fusel acid (for example phenylacetate) NADH

Oxidative branch producing fusel acids such as phenylacetate, 2-methylbutanoate and 4-hydroxyphenylacetate. Only the phenylacetaldehyde step has been assigned to a specific gene (ALD3); the isozymes acting on the other fusel aldehydes are not established.

PMID:23836015
Ald3 is mainly responsible for phenylacetaldehyde oxidation.
Ald3 is mainly responsible for phenylacetaldehyde oxidation