Alcoholic fermentation of pyruvate to ethanol

Alcoholic fermentation converts pyruvate to acetaldehyde and carbon dioxide, then reduces acetaldehyde to ethanol while oxidizing NADH to NAD+. The terminal branch regenerates reducing-cofactor balance without itself producing ATP; upstream ATP yield depends on the glycolytic route. Canonical thiamine-dependent pyruvate decarboxylases operate in fungi, plants and selected bacteria, while Carassius fish possess a separately evolved mitochondrial E1-derived implementation. Zinc-dependent medium-chain and group III alcohol dehydrogenases provide distinct reduction catalysts, with metal activation and physiological deployment varying among members. An optional acetoin/butanediol branch diverts carbon through PDC carboligation or the bacterial catabolic acetolactate route.

MODULE:alcoholic_fermentationCOMPLETEABSTRACTMetabolic Pathwaymodules/alcoholic_fermentation.yaml

pyruvate fermentation to ethanolGO:0019655

GO:0019655

pyruvate fermentation to ethanol

Module-level process. Its definition, the anaerobic breakdown of pyruvate into ethanol and CO2, matches the module boundary exactly.

GO:0034079

butanediol biosynthetic process

Concept for the optional side branch. GO places it under pyruvate fermentation and lists acetolactate synthase, acetolactate decarboxylase and diacetyl reductase as parts, which is the bacterial route modelled here as a variant.

YeastPathways:GLUCFERMEN-PWY

superpathway of glucose fermentation

Superpathway = EMP glycolysis (modules/emp_glycolysis.yaml) + this module + the PDH-bypass aldehyde dehydrogenases (modules/pdh_bypass_acetyl_coa_synthesis.yaml). From its catalyst lists, PDC1/PDC5/PDC6 (RXN-6161) and ADH1 (ALCOHOL-DEHYDROG-RXN) are kept here. ADH2-ADH5 are listed for the ADH reaction, but ADH2 is the glucose-repressed ethanol-oxidising isozyme (PDH bypass / ethanol utilisation), ADH3 is a mitochondrial redox-shuttle enzyme, and ADH4 and ADH5 are minor. FBP1 and the ALD reactions in the frame are not fermentation steps.

YeastPathways:PWY3O-440

pyruvate fermentation to acetoin III

Source for the pyruvate-decarboxylase carboligation side reactions (2 acetaldehyde to acetoin, RXN3O-470; pyruvate + acetaldehyde to acetoin, RXN0-2022), both assigned to PDC1/PDC5/PDC6.

YeastPathways:PWY3O-335

acetoin biosynthesis

Acetolactate-derived acetoin: ILV2/ILV6 acetohydroxyacid synthase makes (S)-2-acetolactate, which decomposes non-enzymatically by oxidative decarboxylation to diacetyl, and BDH1 reduces diacetyl to acetoin. In yeast the acetolactate synthase is the mitochondrial branched-chain amino acid enzyme and diacetyl formation is a spill-over. It is therefore recorded in notes and not counted as a member. The bacterial catabolic acetolactate route (with an acetolactate decarboxylase) is modelled as a variant instead.

YeastPathways:PWY3O-981

superpathway of acetoin and butanediol biosynthesis

Union of PWY3O-440, PWY3O-335 and the BDH1 acetoin reduction.

YeastPathways:PWY3O-661

butanediol biosynthesis

Single-reaction frame for BDH1 (R)-acetoin reduction to (R,R)-2,3-butanediol; folded into the side branch.

YeastPathways:PWY3O-246

(R,R)-butanediol degradation

The same BDH1 reaction in the oxidative direction (growth on butanediol). This catabolic use is outside the fermentation boundary and is recorded only as the reverse of the side-branch step.

PMID:8904337

Pyruvate decarboxylase: an indispensable enzyme for growth of Saccharomyces cerevisiae on glucose.

PDC1, PDC5 and PDC6 each encode an active pyruvate decarboxylase.

In Saccharomyces cerevisiae, the structural genes PDC1, PDC5 and PDC6 each encode an active pyruvate decarboxylase.

PMID:2404950

pdc1(0) mutants of Saccharomyces cerevisiae give evidence for an additional structural PDC gene: cloning of PDC5, a gene homologous to PDC1.

PDC5 supplies the remaining activity when PDC1 is deleted, with PDC1 subject to autoregulation.

The resulting pdc1(0) mutants were able to grow on glucose and still contained 60 to 70% of the wild-type PDC activity.

PMID:15864308

Resurrecting ancestral alcohol dehydrogenases from yeast.

Adh1 reduces acetaldehyde to ethanol during fermentation; its paralog Adh2 oxidises the accumulated ethanol later.

Pyruvate loses carbon dioxide to produce acetaldehyde, which is reduced by alcohol dehydrogenase 1 (Adh1) to ethanol, which accumulates.

PMID:11152939

Stoichiometry and compartmentation of NADH metabolism in Saccharomyces cerevisiae.

Alcoholic fermentation is the first of the NADH-reoxidation routes of yeast.

At least five mechanisms of NADH reoxidation exist in S. cerevisiae.

PMID:6383467

Brewers' yeast pyruvate decarboxylase produces acetoin from acetaldehyde: a novel tool to study the mechanism of steps subsequent to carbon dioxide loss.

Pyruvate decarboxylase forms acetoin as a 3-4% side product and condenses acetaldehyde to acetoin.

Employing this method enabled the demonstration of the catalysis of acetaldehyde condensation to acetoin by the enzyme.

PMID:10938079

Characterization of a (2R,3R)-2,3-butanediol dehydrogenase as the Saccharomyces cerevisiae YAL060W gene product. Disruption and induction of the gene.

BDH1 (YAL060W) is an NAD-dependent (2R,3R)-2,3-butanediol dehydrogenase that reduces acetoin.

In the presence of NADH, it could catalyze the stereospecific reduction of racemic acetoin

PMID:11306064

Characterization and functional role of Saccharomyces cerevisiae 2,3-butanediol dehydrogenase.

Other enzymes besides BDH1 can metabolise 2,3-butanediol in yeast.

This suggests that other enzymes, in addition to BDH, can also metabolize 2,3-butanediol in yeast.

PMID:25102102

A metabolic strategy to enhance long-term survival by Phx1 through stationary phase-specific pyruvate decarboxylases in fission yeast.

Fission yeast has four predicted pyruvate decarboxylases; pdc201 and pdc202 are induced by Phx1 in stationary phase.

Among the four predicted genes for pyruvate decarboxylase, only the Phx1-dependent genes (pdc201+ and pdc202+) contributed to long-term survival

PMID:15040954

A distinct type of alcohol dehydrogenase, adh4+, complements ethanol fermentation in an adh1-deficient strain of Schizosaccharomyces pombe.

Fission-yeast adh1 is the main fermentative ADH, and the ADH4-like adh4 can replace it. Ethanol fermentation therefore runs through either ADH family.

Since the strain lacking both adh1 and adh4 genes (delta adh1 delta adh4) showed non-fermentative retarded growth, only these two ADHs produce ethanol for fermentative growth.

18Nodes

7Parts

4Variant Sets

10Variants

11Annotons

4Connections

Derived QC

Recommended-field compliance

97.6% recommended fields populated

knowledge_gaps[0].provenance[0] · reference_section_type (0/1)

Module deep research

✗ none found

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

Leaf nodes lacking representative members

✓ representative grounding skipped for abstract module.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

21 gene-function check(s) reflected in core functions · 0 conflict(s) · 15 evidence or coverage gap(s) (45 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.

Annoton	Participant	Function	Assessment
pdc_activity	PDC1 (S. cerevisiae) UniProtKB:P06169 Family Representative	pyruvate decarboxylase activity GO:0004737	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdc_activity	PDC5 (S. cerevisiae) UniProtKB:P16467 Family Representative	pyruvate decarboxylase activity GO:0004737	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdc_activity	PDC6 (S. cerevisiae) UniProtKB:P26263 Family Representative	pyruvate decarboxylase activity GO:0004737	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdc_activity	pdc101 (S. pombe) UniProtKB:Q92345 Family Representative	pyruvate decarboxylase activity GO:0004737	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdc_activity	pdc102 (S. pombe) UniProtKB:Q9P7P6 Family Representative	pyruvate decarboxylase activity GO:0004737	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdc_activity	pdc201 (S. pombe) UniProtKB:O42873 Family Representative	pyruvate decarboxylase activity GO:0004737	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdc_activity	pdc202 (S. pombe) UniProtKB:Q09737 Family Representative	pyruvate decarboxylase activity GO:0004737	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdc_activity	pdc (Zymomonas mobilis ZM4) UniProtKB:P06672 Family Representative	pyruvate decarboxylase activity GO:0004737	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdc_activity	PDC1 (Arabidopsis thaliana) UniProtKB:O82647 Family Representative	pyruvate decarboxylase activity GO:0004737	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
carassius_pdc_activity	PROTEIN_COMPLEX Gene	pyruvate decarboxylase activity GO:0004737	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
carassius_pdc_activity/carassius_alpha3	E1alpha3 (Carassius carassius) UniProtKB:A0A288DRL8 Family Representative	contribution to the muscle E1alpha3/E1beta2 pyruvate decarboxylase complex No function ID	No Function Id A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
carassius_pdc_activity/carassius_beta2	E1beta2 (Carassius carassius) UniProtKB:A0A288DUG2 Family Representative	contribution to the muscle E1alpha3/E1beta2 pyruvate decarboxylase complex No function ID	No Function Id A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
zinc_adh_activity	ADH1 (S. cerevisiae) UniProtKB:P00330 Family Representative	ethanol dehydrogenase (NAD+) activity GO:0120542	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
zinc_adh_activity	adh1 (S. pombe) UniProtKB:P00332 Family Representative	ethanol dehydrogenase (NAD+) activity GO:0120542	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
zinc_adh_activity	ADH1 (Arabidopsis thaliana) UniProtKB:P06525 Family Representative	ethanol dehydrogenase (NAD+) activity GO:0120542	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
iron_adh_activity	adhB (Zymomonas mobilis ZM4) UniProtKB:P0DJA2 Family Representative	ethanol dehydrogenase (NAD+) activity GO:0120542	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
iron_adh_activity	adh4 (S. pombe) UniProtKB:Q09669 Family Representative	ethanol dehydrogenase (NAD+) activity GO:0120542	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
iron_adh_activity	ADH4 (S. cerevisiae) UniProtKB:P10127 Family Representative	ethanol dehydrogenase (NAD+) activity GO:0120542	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bacterial_zinc_adh_activity	adhA (Zymomonas mobilis ZM4) UniProtKB:P20368 Family Representative	ethanol dehydrogenase (NAD+) activity GO:0120542	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fish_adh8a_activity	ADH8a3 (Carassius carassius) UniProtKB:A0A1P7XEJ9 Family Representative	ethanol dehydrogenase (NAD+) activity GO:0120542	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdc_carboligase_activity	PDC1 (S. cerevisiae) UniProtKB:P06169 Family Representative	acetaldehyde carboligation to acetoin (pyruvate decarboxylase side reaction) No function ID	No Function Id A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
pdc_carboligase_activity	PDC5 (S. cerevisiae) UniProtKB:P16467 Family Representative	acetaldehyde carboligation to acetoin (pyruvate decarboxylase side reaction) No function ID	No Function Id A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
pdc_carboligase_activity:required_function	PDC1 (S. cerevisiae) UniProtKB:P06169 Family Representative	acetaldehyde carboligation to acetoin No function ID	No Function Id A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
pdc_carboligase_activity:required_function	PDC5 (S. cerevisiae) UniProtKB:P16467 Family Representative	acetaldehyde carboligation to acetoin No function ID	No Function Id A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
catabolic_als_activity	alsS (Bacillus subtilis 168) UniProtKB:Q04789 Family Representative	acetolactate synthase activity GO:0003984	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aldc_activity	alsD (Bacillus subtilis 168) UniProtKB:Q04777 Family Representative	acetolactate decarboxylase activity GO:0047605	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bdh_activity	BDH1 (S. cerevisiae) UniProtKB:P39714 Family Representative	(R,R)-butanediol dehydrogenase activity GO:0000721	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bacterial_bdh_activity	bdhA (Bacillus subtilis 168) UniProtKB:O34788 Family Representative	(R,R)-butanediol dehydrogenase activity GO:0000721	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdc_activity	thiamine-diphosphate-dependent pyruvate decarboxylase PANTHER:PTHR43452:SF30 Family	pyruvate decarboxylase activity GO:0004737	Family Supported Family review supports GO:0004737 for PANTHER:PTHR43452:SF30. Safe for the canonical PDC subfamilies, which include the yeast PDC1/PDC5/PDC6 (SF30), the Zymomonas/Neurospora/fission-yeast pdc101/pdc102 group (SF1), fission yeast pdc201 (SF36) and the plant PDC subfamilies. Not safe for SF3 (ARO10, experimentally lacking pyruvate activity). Within SF30, THI3 is an exception, and the bacterial IpdC/Kdc members of SF30 were not assessed here and should not be assumed to be pyruvate decarboxylases on subfamily grounds. This is the term the alcoholic fermentation and PDH bypass modules require of the family.
pdc_activity	thiamine-diphosphate-dependent pyruvate decarboxylase PANTHER:PTHR43452:SF1 Family	pyruvate decarboxylase activity GO:0004737	Family Supported Family review supports GO:0004737 for PANTHER:PTHR43452:SF1. Safe for the canonical PDC subfamilies, which include the yeast PDC1/PDC5/PDC6 (SF30), the Zymomonas/Neurospora/fission-yeast pdc101/pdc102 group (SF1), fission yeast pdc201 (SF36) and the plant PDC subfamilies. Not safe for SF3 (ARO10, experimentally lacking pyruvate activity). Within SF30, THI3 is an exception, and the bacterial IpdC/Kdc members of SF30 were not assessed here and should not be assumed to be pyruvate decarboxylases on subfamily grounds. This is the term the alcoholic fermentation and PDH bypass modules require of the family.
pdc_activity	thiamine-diphosphate-dependent pyruvate decarboxylase PANTHER:PTHR43452:SF36 Family	pyruvate decarboxylase activity GO:0004737	Family Supported Family review supports GO:0004737 for PANTHER:PTHR43452:SF36. Safe for the canonical PDC subfamilies, which include the yeast PDC1/PDC5/PDC6 (SF30), the Zymomonas/Neurospora/fission-yeast pdc101/pdc102 group (SF1), fission yeast pdc201 (SF36) and the plant PDC subfamilies. Not safe for SF3 (ARO10, experimentally lacking pyruvate activity). Within SF30, THI3 is an exception, and the bacterial IpdC/Kdc members of SF30 were not assessed here and should not be assumed to be pyruvate decarboxylases on subfamily grounds. This is the term the alcoholic fermentation and PDH bypass modules require of the family.
pdc_activity	thiamine-diphosphate-dependent pyruvate decarboxylase PANTHER:PTHR43452:SF18 Family	pyruvate decarboxylase activity GO:0004737	Family Supported Family review supports GO:0004737 for PANTHER:PTHR43452:SF18. Safe for the canonical PDC subfamilies, which include the yeast PDC1/PDC5/PDC6 (SF30), the Zymomonas/Neurospora/fission-yeast pdc101/pdc102 group (SF1), fission yeast pdc201 (SF36) and the plant PDC subfamilies. Not safe for SF3 (ARO10, experimentally lacking pyruvate activity). Within SF30, THI3 is an exception, and the bacterial IpdC/Kdc members of SF30 were not assessed here and should not be assumed to be pyruvate decarboxylases on subfamily grounds. This is the term the alcoholic fermentation and PDH bypass modules require of the family.
carassius_alpha3	E1alpha3-containing E1-derived subunit lineage PANTHER:PTHR11516:SF60 Family	contribution to the muscle E1alpha3/E1beta2 pyruvate decarboxylase complex No function ID	No Function Id The family function has no GO identifier for comparison; prose is not matched.
carassius_beta2	E1beta2-containing E1-derived subunit lineage PANTHER:PTHR11624:SF96 Family	contribution to the muscle E1alpha3/E1beta2 pyruvate decarboxylase complex No function ID	No Function Id The family function has no GO identifier for comparison; prose is not matched.
zinc_adh_activity	zinc-containing medium-chain alcohol dehydrogenase PANTHER:PTHR42940:SF3 Family	ethanol dehydrogenase (NAD+) activity GO:0120542	Family Supported Family review supports GO:0120542 for PANTHER:PTHR42940:SF3. The term both modules require of this family. Established for the fungal ADH1 group (SF3: ADH1 fermentative direction, ADH2 oxidative direction, ADH3 mitochondrial, fission yeast adh1) and plausible for SF5 alcB, a PAINT seed for the fungal ADH node. Not safe for SF7 (secondary-metabolism dehydrogenases) or SF8 as a whole (contains CoA-thioester reductases). ADH5 is an active but minor isozyme and is annotated only to the parent alcohol dehydrogenase activity in its review.
zinc_adh_activity	zinc-containing medium-chain alcohol dehydrogenase PANTHER:PTHR43880:SF26 Family	ethanol dehydrogenase (NAD+) activity GO:0120542	Family Supported Family review supports GO:0120542 for PANTHER:PTHR43880:SF26. The alcoholic fermentation module lists PTHR43880 as a family_term for the plant zinc fermentative ADH (Arabidopsis ADH1) with a GO:0120542 required_function filter. Ethanol dehydrogenation belongs to the derived classes: plant class P (SF26, SF9, SF40, SF59) and the vertebrate class I subfamilies. Class III enzymes (SF12, SF4, SF58), including SFA1, are not fermentative ethanol dehydrogenases, so the family-level term must be filtered as the module does. The vertebrate class I subfamilies are listed for completeness; they oxidise ethanol in liver but are not part of fermentation.
iron_adh_activity	group III alcohol dehydrogenase (member-specific metal activation) PANTHER:PTHR11496:SF102 Family	ethanol dehydrogenase (NAD+) activity GO:0120542	Family Function Unreviewed Family review leaves GO:0120542 UNRESOLVED. Positive support is retained for the ADH4/AdhB enzymes in SF102 and for Salmonella LT2 EutG P41795 in SF94. The latter has native physiological evidence for acetaldehyde reduction and NAD recycling, not purified target kinetics. The official tree places P41795 and E. coli P76553 in SF94, but the former SF102-only restriction wrongly excluded this positive member. SF102 itself mixes substrate specificities, and no whole-SF94 kinetic or residue-level conservation claim is made. Thus neither a family-wide nor an exhaustive whole-subfamily grant expresses the experimentally bounded scope. The exact prior judgment and complete original review are archived in source-analysis/ethanolamine-scope-reassessment.json; this uncertainty concerns scope, not rejection of the positive members.
bacterial_zinc_adh_activity	ethanol-active bacterial AdhA-like zinc alcohol dehydrogenases Family	ethanol dehydrogenase (NAD+) activity GO:0120542	Family Id Missing The family has no identifier linking it to a curated family review.
fish_adh8a_activity	ethanol-active ADH8a-like zinc alcohol dehydrogenases Family	ethanol dehydrogenase (NAD+) activity GO:0120542	Family Id Missing The family has no identifier linking it to a curated family review.
pdc_carboligase_activity	thiamine-diphosphate-dependent pyruvate decarboxylase PANTHER:PTHR43452:SF30 Family	acetaldehyde carboligation to acetoin (pyruvate decarboxylase side reaction) No function ID	No Function Id The family function has no GO identifier for comparison; prose is not matched.
pdc_carboligase_activity:required_function	thiamine-diphosphate-dependent pyruvate decarboxylase PANTHER:PTHR43452:SF30 Family	acetaldehyde carboligation to acetoin No function ID	No Function Id The family function has no GO identifier for comparison; prose is not matched.
catabolic_als_activity	thiamine-diphosphate enzyme family (catabolic ALS) PANTHER:PTHR18968:SF129 Family	acetolactate synthase activity GO:0003984	Family Supported Family review supports GO:0003984 for PANTHER:PTHR18968:SF129. The alcoholic fermentation module requires this of the family for the catabolic ALS (AlsS). Safe for the catabolic ALS subfamily SF129 and the anabolic AHAS large-subunit subfamilies (SF13, SF170, SF142). Not safe for SF14 (glyoxylate carboligase, already IRD-pruned), SF133, SF9 or SF166. Within SF13, Pseudomonas AruI is named a 2-ketoarginine decarboxylase and should not be assumed to be an ALS.
aldc_activity	alpha-acetolactate decarboxylase PANTHER:PTHR35524:SF1 Family	acetolactate decarboxylase activity GO:0047605	Family Supported Family review supports GO:0047605 FAMILY_WIDE. The term the alcoholic fermentation module requires of this family (AlsD). The family is a single PANTHER subfamily of alpha-acetolactate decarboxylases with no known divergent member.
bdh_activity	zinc medium-chain polyol dehydrogenase (sorbitol dehydrogenase family) PANTHER:PTHR43161:SF23 Family	(R,R)-butanediol dehydrogenase activity GO:0000721	Family Function Unreviewed Family review leaves GO:0000721 UNRESOLVED. The activity is established for fungal BDH1 in SF23 and for bacterial B. subtilis BdhA (O34788) in SF26. The PAINT snapshot independently seeds the bacterial assertion at PTN001707533 from O34788. Thus an exclusive SF23 scope incorrectly excludes an experimentally characterized member. Conversely, the heterogeneous SF26 is not granted this activity as a whole. The complete family boundary is unresolved at the subfamily granularity available here; this does not express uncertainty about the assayed BDH1 or BdhA activities. Retain their gene-level evidence and the module's narrower function-filtered bacterial descriptor rather than inventing a discriminating residue or treating a member_exceptions entry (which denotes loss) as a positive allowance.
bacterial_bdh_activity	BdhA-like bacterial R,R-butanediol dehydrogenases Family	(R,R)-butanediol dehydrogenase activity GO:0000721	Family Id Missing The family has no identifier linking it to a curated family review.

Gene-review completeness (23/23 grounded genes reviewed)

11 complete review(s) · 6 with deep research · 0 missing review · 17 reviewed but lacking deep research

Gene	Review	Complete	Deep research
A0A288DRL8 A0A288DRL8	✓	0/3	✗
A0A288DUG2 A0A288DUG2	✓	1/3	✗
ADH1 P00330	✓	58/60	✓
adh1 P00332	✓	✓	✗
ADH1 P06525	✓	50/52	✗
ADH4 P10127	✓	35/43	✓
adh4 Q09669	✓	✓	✗
ADH8a3 A0A1P7XEJ9	✓	4/6	✗
adhA P20368	✓	✓	✗
adhB P0DJA2	✓	✓	✗
alsD Q04777	✓	✓	✗
alsS Q04789	✓	8/9	✗
BDH1 P39714	✓	✓	✓
bdhA O34788	✓	✓	✗
pdc P06672	✓	5/6	✗
PDC1 O82647	✓	12/14	✗
PDC1 P06169	✓	54/59	✓
pdc101 Q92345	✓	✓	✗
pdc102 Q9P7P6	✓	✓	✗
pdc201 O42873	✓	✓	✗
pdc202 Q09737	✓	✓	✗
PDC5 P16467	✓	58/60	✓
PDC6 P26263	✓	47/52	✓

Tree

Alcoholic fermentation (pyruvate to ethanol)Metabolic Pathwayalcoholic_fermentation

Parts
1. 1. non-oxidative decarboxylation of pyruvate
2. Pyruvate to acetaldehyde + CO2Reactionpdc_step
  
  Variants
  1. Distinct pyruvate-decarboxylating implementations by enzyme ancestry and taxon (One Or More)
    
    Canonical thiamine-dependent pyruvate decarboxylaseReactioncanonical_pdc_variant
    
    Annotons
    
    Pyruvate decarboxylase Family: thiamine-diphosphate-dependent pyruvate decarboxylase
    
    Carassius E1-derived mitochondrial decarboxylaseReactioncarassius_pdc_variant
    
    Annotons
    
    Inferred E1alpha3/E1beta2 decarboxylase Protein Complex: muscle E1alpha3/E1beta2-derived decarboxylase
3. 2. NADH-dependent reduction of acetaldehyde
4. Acetaldehyde + NADH to ethanol + NAD+Reactionadh_step
  
  Variants
  1. Fermentative alcohol dehydrogenase families by enzyme family (One Or More)
    
    Zinc-dependent medium-chain ADH (ADH1 type)Reactionzinc_adh_variant
    
    Annotons
    
    Zinc alcohol dehydrogenase (fermentative) Family: zinc-containing medium-chain alcohol dehydrogenase
    
    Group III ADH implementationReactioniron_adh_variant
    
    Annotons
    
    Group III alcohol dehydrogenase Family: group III alcohol dehydrogenase (member-specific metal activation)
    
    ethanol-active bacterial AdhA-like zinc alcohol dehydrogenasesReactionbacterial_zinc_adh_variant
    
    Annotons
    
    ethanol-active bacterial AdhA-like zinc alcohol dehydrogenases Family: ethanol-active bacterial AdhA-like zinc alcohol dehydrogenases
    
    ethanol-active ADH8a-like zinc alcohol dehydrogenasesReactionfish_adh8a_variant
    
    Annotons
    
    ethanol-active ADH8a-like zinc alcohol dehydrogenases Family: ethanol-active ADH8a-like zinc alcohol dehydrogenases
5. 3. acetoin and 2,3-butanediol side branch optional
6. Acetoin and (R,R)-2,3-butanediol formationMetabolic Pathwaybutanediol_branch
  
  Parts
  1. 1. acetoin formation
  2. Two-carbon units to acetoinMetabolic Pathwayacetoin_formation
    
    Variants
    
    Acetoin-forming routes by route variant (One Or More)
    
    Pyruvate decarboxylase carboligation (yeasts)Reactionpdc_carboligation_variant
    
    Annotons
    
    Pyruvate decarboxylase acting as acyloin-forming carboligase Family: thiamine-diphosphate-dependent pyruvate decarboxylase
    
    Catabolic acetolactate route (bacteria)Metabolic Pathwayacetolactate_route_variant
    
    Parts
    
    1. pyruvate condensation
    
    2 pyruvate to (S)-2-acetolactate + CO2Reactioncatabolic_als_step
    
    Annotons
    
    Catabolic acetolactate synthase (AlsS) Family: thiamine-diphosphate enzyme family (catabolic ALS)
    
    2. acetolactate decarboxylation
    
    (S)-2-acetolactate to (R)-acetoin + CO2Reactionaldc_step
    
    Annotons
    
    Acetolactate decarboxylase (AlsD) Family: alpha-acetolactate decarboxylase
  3. 2. acetoin reduction
  4. (R)-acetoin + NADH to (R,R)-2,3-butanediol + NAD+Reactionbdh_step
    
    Variants
    
    R,R-butanediol dehydrogenase implementations by functional lineage (One Or More)
    
    Fungal Bdh1Reactionyeast_bdh_variant
    
    Annotons
    
    (R,R)-butanediol dehydrogenase Family: zinc medium-chain polyol dehydrogenase (sorbitol dehydrogenase family)
    
    Bacterial BdhAReactionbacterial_bdh_variant
    
    Annotons
    
    Bacterial R,R-butanediol dehydrogenase Family: BdhA-like bacterial R,R-butanediol dehydrogenases

Details

Context

BacteriaNCBITaxon:2 EukaryotaNCBITaxon:2759

The root is an evidence envelope, not a claim of ancestral presence in every descendant. Each variant constrains its physiological and taxonomic use. No universal compartment is asserted.

Alcoholic fermentation (pyruvate to ethanol)Metabolic Pathwayalcoholic_fermentation

pyruvate -> acetaldehyde + CO2 -> ethanol (NADH -> NAD+); optional side branch acetaldehyde/pyruvate -> acetoin -> (R,R)-2,3-butanediol.

pyruvate fermentation to ethanolGO:0019655

Context

BacteriaNCBITaxon:2 EukaryotaNCBITaxon:2759

The root is an evidence envelope, not a claim of ancestral presence in every descendant. Each variant constrains its physiological and taxonomic use. No universal compartment is asserted.

Boundary: direct pyruvate decarboxylation followed by acetaldehyde reduction, plus the existing optional acetoin/R,R-butanediol branch. Upstream glycolysis, cofactor synthesis, pyruvate-formate lyase/AdhE routes, PDH bypass, glycerol formation and Ehrlich chemistry remain separate. The terminal ethanol branch produces no ATP; EMP-fed yeast and ED-fed Zymomonas have different upstream yields. Taxa are an evidence envelope, not a distribution or universal ancestral-presence claim. Representative physiology is conditional. PDC6 can support partial glucose fermentation after promoter activation. Group III ADH does not imply iron activation in every member. Carassius subunit-level decarboxylase assignment is inferred and its beta2 accession is an incomplete submitted sequence, not evidence of native truncation. Plant ADH1 does not explain all ethanol production in mutants. The optional branch models a defined R,R endpoint, not all stereoisomer outputs in Klebsiella, Serratia or Bacillus. In yeast, leaked biosynthetic acetolactate can form diacetyl nonenzymatically and Bdh1 can reduce it; the mitochondrial ILV2/ILV6 precursor pathway is not a native catabolic AlsS substitute. The current leaf carboligation activity lacks a specific GO term and is kept as explicit chemistry. Production GO-CAM associations are organism-specific. PomBase model 678073a900000393 supplies the four PDC activities and adh1; its regulator, cofactor-supply, glycolytic and acetate-producing nodes lie outside this module. Broad secondary-alcohol process annotations and GO:0019152 for Bdh1 diacetyl reduction are not intrinsically incorrect merely because a reaction can be written in the opposite direction. Additional imported-model discrepancies are documented in audit notes after source verification.

Connections

pdc_step -> adh_step Provides Input For

Acetaldehyde from the decarboxylase is the ADH substrate.

PMID:12857811

Plant PDC overexpression raises acetaldehyde and downstream ethanol.

ADH (EC 1.1.1.1) then converts acetaldehyde to ethanol

PMID:35050092

Review states the PDC-to-ADH acetaldehyde sequence.

PMID:28801642

Carassius muscle physiology supports the compartment-crossing acetaldehyde-to-ethanol sequence; a specific transporter is not asserted.

pdc_step -> pdc_carboligation_variant Provides Input For

PDC-derived acetaldehyde can feed the yeast carboligation branch; the bacterial AlsS route independently starts from pyruvate.

PMID:6383467

PDC catalyzes acetaldehyde condensation to acetoin.

Part 1: non-oxidative decarboxylation of pyruvate

Pyruvate to acetaldehyde + CO2Reactionpdc_step

Variant set: Distinct pyruvate-decarboxylating implementations by enzyme ancestry and taxon (One Or More)

Canonical thiamine-dependent pyruvate decarboxylaseReactioncanonical_pdc_variant

Context

FungiNCBITaxon:4751 EmbryophytaNCBITaxon:3193 BacteriaNCBITaxon:2

Native examples are Saccharomyces, Schizosaccharomyces, Arabidopsis and Zymomonas; this is not a claim of ubiquitous canonical PDC.

Annotons

Pyruvate decarboxylase

pdc_activity

Participant: Family: thiamine-diphosphate-dependent pyruvate decarboxylase

Family:

thiamine-diphosphate-dependent pyruvate decarboxylase

Representative Members: PDC1 (S. cerevisiae)UniProtKB:P06169 PDC5 (S. cerevisiae)UniProtKB:P16467 PDC6 (S. cerevisiae)UniProtKB:P26263 pdc101 (S. pombe)UniProtKB:Q92345 pdc102 (S. pombe)UniProtKB:Q9P7P6 pdc201 (S. pombe)UniProtKB:O42873 pdc202 (S. pombe)UniProtKB:Q09737 pdc (Zymomonas mobilis ZM4)UniProtKB:P06672 PDC1 (Arabidopsis thaliana)UniProtKB:O82647

Required Function:

pyruvate decarboxylase activityGO:0004737

Function

pyruvate decarboxylase activityGO:0004737

Substrates: pyruvate

Products: acetaldehyde CO2

The irreversible decarboxylation step that diverts pyruvate away from the pyruvate dehydrogenase complex. In yeasts the same acetaldehyde also feeds the PDH bypass (modules/pdh_bypass_acetyl_coa_synthesis.yaml). PDC-null mutants fail to grow in defined medium with glucose as sole carbon source, while complex glucose medium permits slower growth (PMID:8904337); the acetyl-CoA supply role must be distinguished from fermentative NADH recycling. The yeast isozymes also decarboxylate branched-chain 2-oxo acids (Ehrlich pathway), which is outside this module. ARO10 and the TPP-sensing regulator THI3 are PDC-family members that do not decarboxylate pyruvate and are not members here. Localization is supported for fungal and plant exemplars, but no direct native ZM4 localization assay is asserted. Fission-yeast isozyme genetics and total PDC activity do not constitute purified kinetic characterization of each paralog.

PMID:8904337

Each budding-yeast PDC isozyme encodes an active enzyme; total loss compromises glucose metabolism.

PMID:1807827

PDC6 can support partial fermentation when expression is increased.

PMID:25102102

Fission-yeast induction, mutant phenotypes and total enzyme measurements distinguish isozyme deployment.

PMID:12857811

Arabidopsis PDC overexpression increases acetaldehyde and ethanol production.

PMID:3546263

Purified Zymomonas enzyme and cloned-gene expression establish pyruvate decarboxylation.

Carassius E1-derived mitochondrial decarboxylaseReactioncarassius_pdc_variant

Context

CarassiusNCBITaxon:7956

skeletal muscle

anoxia

Annotons

Inferred E1alpha3/E1beta2 decarboxylase

carassius_pdc_activity

Participant: Protein Complex: muscle E1alpha3/E1beta2-derived decarboxylase

Protein Complex:

muscle E1alpha3/E1beta2-derived decarboxylase

Active units:

E1alpha3

Participant: Family: E1alpha3-containing E1-derived subunit lineage

Family:

E1alpha3-containing E1-derived subunit lineagePANTHER:PTHR11516:SF60 PANTHER membership establishes ancestry, not a universal decarboxylase function. Conventional PDH members in this family are not ethanol-pathway exemplars.

Representative Members: E1alpha3 (Carassius carassius)UniProtKB:A0A288DRL8

Required Function:

contribution to the muscle E1alpha3/E1beta2 pyruvate decarboxylase complex A contributing subunit role, not independent enabling of the whole reaction. Excludes conventional E1 members serving only lipoyl-E2 acetylation.

Taxon:

CarassiusNCBITaxon:7956

Role: Inferred contributing subunit of the E1-derived pyruvate decarboxylase

PMID:28801642

Expression, sequence comparison, E1 localization and interface modeling support the specialized alpha3/beta2 pair; no purified-pair reconstitution is asserted.

E1beta2

Participant: Family: E1beta2-containing E1-derived subunit lineage

Family:

E1beta2-containing E1-derived subunit lineagePANTHER:PTHR11624:SF96 PANTHER membership establishes ancestry, not a universal decarboxylase function. Conventional PDH members in this family are not ethanol-pathway exemplars.

Representative Members: E1beta2 (Carassius carassius)UniProtKB:A0A288DUG2

Required Function:

Taxon:

CarassiusNCBITaxon:7956

Role: Inferred contributing subunit of the E1-derived pyruvate decarboxylase

PMID:28801642

Expression, sequence comparison, E1 localization and interface modeling support the specialized alpha3/beta2 pair; no purified-pair reconstitution is asserted.

Function

pyruvate decarboxylase activityGO:0004737

Substrates: pyruvate

Products: acetaldehyde CO2

Locations

mitochondrionGO:0005739

Mitochondrial acetaldehyde production in Carassius muscle is established physiologically. Assignment to a separate alpha3/beta2 complex is an integrated inference, not a purified complex assay; residual PDH acetyltransfer chemistry is unresolved. The shared molecular function does not imply canonical-PDC family ancestry.

PMID:28801642

Primary comparative study supports a separately evolved mitochondrial E1-derived implementation, with paralog-specific enzymology still inferred.

Part 2: NADH-dependent reduction of acetaldehyde

Acetaldehyde + NADH to ethanol + NAD+Reactionadh_step

The redox-balancing step. Two unrelated enzyme families do it, so it is modelled as a variant set on enzyme family. Both carry the same GO molecular function.

Variant set: Fermentative alcohol dehydrogenase families by enzyme family (One Or More)

ONE_OR_MORE: Zymomonas carries both native enzyme classes; fission yeast compensates for adh1 loss using adh4. Family membership alone does not fix metal preference or physiological compartment.

Zinc-dependent medium-chain ADH (ADH1 type)Reactionzinc_adh_variant

Annotons

Zinc alcohol dehydrogenase (fermentative)

zinc_adh_activity

Participant: Family: zinc-containing medium-chain alcohol dehydrogenase

Family:

zinc-containing medium-chain alcohol dehydrogenase Fungal ADH1-type and plant class-P enzymes support this role. Broader bacterial AdhA and fish ADH8a lineages are modeled separately because the reviewed PANTHER functional scopes do not establish their exact activity-defined subgroup.

Representative Members: ADH1 (S. cerevisiae)UniProtKB:P00330 adh1 (S. pombe)UniProtKB:P00332 ADH1 (Arabidopsis thaliana)UniProtKB:P06525

Required Function:

ethanol dehydrogenase (NAD+) activityGO:0120542

Function

ethanol dehydrogenase (NAD+) activityGO:0120542

Substrates: acetaldehyde NADH

Products: ethanol NAD(+)

Regenerates NAD+ by acetaldehyde reduction. Cytosolic placement is supported for yeast/plant examples and inferred for fish ADH8a3 from family context, not directly measured for every representative. The physiological direction depends on isozyme and condition. Arabidopsis ADH1 contributes to hypoxic fermentation, but substantial residual ethanol in adh1 mutants demonstrates additional enzymatic routes.

PMID:15864308

Yeast Adh1 is physiologically associated with ethanol production, contrasted with Adh2 ethanol use.

PMID:15040954

S. pombe adh1 is the main fermentative isozyme.

PMID:2935393

Zymomonas isozyme biochemistry distinguishes zinc AdhA and iron AdhB and their reaction-direction contributions.

PMID:30861072

Arabidopsis ADH1 is not the sole source of hypoxic ethanol production.

PMID:28801642

Carassius ADH8a3 expression dominates skeletal muscle ADH8a transcripts.

PMID:15231826

Purified zebrafish ADH8A metabolizes ethanol; this is comparator, not carp target kinetics.

Group III ADH implementationReactioniron_adh_variant

Annotons

Group III alcohol dehydrogenase

iron_adh_activity

Participant: Family: group III alcohol dehydrogenase (member-specific metal activation)

Family:

group III alcohol dehydrogenase (member-specific metal activation)

Representative Members: adhB (Zymomonas mobilis ZM4)UniProtKB:P0DJA2 adh4 (S. pombe)UniProtKB:Q09669 ADH4 (S. cerevisiae)UniProtKB:P10127

Required Function:

ethanol dehydrogenase (NAD+) activityGO:0120542

Function

ethanol dehydrogenase (NAD+) activityGO:0120542

Substrates: acetaldehyde NADH

Products: ethanol NAD(+)

Zymomonas AdhB is iron-dependent and contributes native fermentation alongside zinc AdhA. S. cerevisiae ADH4 is zinc-activated; its contribution under standard fermentative culture is limited. S. pombe Adh4 can compensate for adh1 loss, whereas a separate study localizes ethanol oxidation to the mitochondrial matrix. The compartment of that compensatory reductive flux is not established.

PMID:21295587

ZM4 AdhB structures establish catalytic iron and bound NAD.

PMID:2935393

Isozyme biochemistry distinguishes oxidation dominance from acetaldehyde-reduction contribution.

PMID:3282541

Purified budding-yeast ADH4 is activated by zinc rather than iron.

PMID:15040954

Fission-yeast adh4 supports compensatory ethanol fermentation.

PMID:16999687

Mitochondrial matrix evidence concerns ethanol oxidation; it does not locate compensatory reductive flux.

ethanol-active bacterial AdhA-like zinc alcohol dehydrogenasesReactionbacterial_zinc_adh_variant

Annotons

ethanol-active bacterial AdhA-like zinc alcohol dehydrogenases

bacterial_zinc_adh_activity

Participant: Family: ethanol-active bacterial AdhA-like zinc alcohol dehydrogenases

Family:

ethanol-active bacterial AdhA-like zinc alcohol dehydrogenases Verified AdhA belongs to PANTHER:PTHR42940:SF8, but that heterogeneous subfamily also contains CoA-thioester reductases. No exact identifier is asserted for the narrower ethanol-active subgroup.

Representative Members: adhA (Zymomonas mobilis ZM4)UniProtKB:P20368

Required Function:

ethanol dehydrogenase (NAD+) activityGO:0120542

Taxon:

BacteriaNCBITaxon:2

Function

ethanol dehydrogenase (NAD+) activityGO:0120542

Substrates: acetaldehyde NADH

Products: ethanol NAD(+)

Verified AdhA belongs to PANTHER:PTHR42940:SF8, but that heterogeneous subfamily also contains CoA-thioester reductases. No exact identifier is asserted for the narrower ethanol-active subgroup. Selection also requires the specified activity and appropriate physiological deployment; broad sequence-family membership alone is insufficient.

PMID:2935393

Native isozyme biochemistry establishes acetaldehyde reduction to ethanol.

PMID:2185223

Cloned adhA sequence distinguishes the zinc-family isozyme from AdhB.

ethanol-active ADH8a-like zinc alcohol dehydrogenasesReactionfish_adh8a_variant

Annotons

ethanol-active ADH8a-like zinc alcohol dehydrogenases

fish_adh8a_activity

Participant: Family: ethanol-active ADH8a-like zinc alcohol dehydrogenases

Family:

ethanol-active ADH8a-like zinc alcohol dehydrogenases Verified target belongs to PANTHER:PTHR43880:SF3. The existing family review does not establish an ethanol-activity scope for the entire subfamily, so no exact identifier is asserted for the narrower functionally supported subgroup.

Representative Members: ADH8a3 (Carassius carassius)UniProtKB:A0A1P7XEJ9

Required Function:

ethanol dehydrogenase (NAD+) activityGO:0120542

Taxon:

CarassiusNCBITaxon:7956

Function

ethanol dehydrogenase (NAD+) activityGO:0120542

Substrates: acetaldehyde NADH

Products: ethanol NAD(+)

Verified target belongs to PANTHER:PTHR43880:SF3. The existing family review does not establish an ethanol-activity scope for the entire subfamily, so no exact identifier is asserted for the narrower functionally supported subgroup. Selection also requires the specified activity and appropriate physiological deployment; broad sequence-family membership alone is insufficient.

PMID:28801642

Muscle ADH8a3 expression and pathway physiology support the inferred ethanol role.

PMID:15231826

Purified zebrafish ADH8A metabolizes ethanol; this comparator is not carp target kinetics.

Part 3: acetoin and 2,3-butanediol side branch (optional)

Acetoin and (R,R)-2,3-butanediol formationMetabolic Pathwaybutanediol_branch

Optional routes to acetoin and the (R,R)-butanediol product, represented in yeast and Bacillus. Different organisms produce different stereoisomer mixtures; this branch does not claim all microbial butanediol synthesis has the same endpoint, or that Bacillus uses the core PDC ethanol route.

butanediol biosynthetic processGO:0034079 acetoin biosynthetic processGO:0045151

PMID:37644496

Comparative review distinguishes BDH families, substrate stereochemistry and species-dependent product mixtures; the modeled R,R route is a defined subset.

PMID:10809684

Native B. subtilis fermentation establishes the acetoin/butanediol branch.

Connections

acetoin_formation -> bdh_step Provides Input For

R-acetoin from the bacterial route or the R component of yeast acetoin feeds the R,R product. This edge does not assert uniform stereochemical output for all acetoin-forming routes.

PMID:18820069

Native bdhA disruption links acetoin consumption to butanediol production.

PMID:10938079

Yeast Bdh1 directly reduces acetoin.

Part 1: acetoin formation

Two-carbon units to acetoinMetabolic Pathwayacetoin_formation

Variant set: Acetoin-forming routes by route variant (One Or More)

Pyruvate decarboxylase carboligation (yeasts)Reactionpdc_carboligation_variant

Annotons

Pyruvate decarboxylase acting as acyloin-forming carboligase

pdc_carboligase_activity

Participant: Family: thiamine-diphosphate-dependent pyruvate decarboxylase

Family:

thiamine-diphosphate-dependent pyruvate decarboxylase

Representative Members: PDC1 (S. cerevisiae)UniProtKB:P06169 PDC5 (S. cerevisiae)UniProtKB:P16467

Required Function:

acetaldehyde carboligation to acetoin

Function

acetaldehyde carboligation to acetoin (pyruvate decarboxylase side reaction)

Substrates: acetaldehyde pyruvate

Products: acetoin CO2

Locations

cytosolGO:0005829

A side reaction of the PDC enamine intermediate. Two acetaldehydes can condense to acetoin, or pyruvate plus acetaldehyde can yield acetoin plus CO2; these are distinct substrate routes. The substrates below encode the pyruvate-plus-acetaldehyde route. The primary brewer-yeast enzyme experiment does not establish identical side flux for every isozyme.

PMID:6383467

Purified brewer-yeast PDC catalyzes acetaldehyde condensation to acetoin; isozyme-specific physiological contributions remain qualified.

Catabolic acetolactate route (bacteria)Metabolic Pathwayacetolactate_route_variant

Context

BacteriaNCBITaxon:2

The complete native sequence is grounded by B. subtilis AlsS, AlsD and BdhA; it is not claimed universal in bacteria.

Connections

catabolic_als_step -> aldc_step Provides Input For

PMID:7685336

Native alsS/alsD operon encodes sequential acetoin production.

PMID:10809684

Physiological fermentation connects acetolactate synthesis and decarboxylation.

Part 1: pyruvate condensation

2 pyruvate to (S)-2-acetolactate + CO2Reactioncatabolic_als_step

Annotons

Catabolic acetolactate synthase (AlsS)

catabolic_als_activity

Participant: Family: thiamine-diphosphate enzyme family (catabolic ALS)

Family:

thiamine-diphosphate enzyme family (catabolic ALS)

Representative Members: alsS (Bacillus subtilis 168)UniProtKB:Q04789

Required Function:

acetolactate synthase activityGO:0003984

Function

acetolactate synthase activityGO:0003984

Substrates: pyruvate

Products: (S)-2-acetolactate CO2

Bacillus catabolic AlsS condenses pyruvate using ThDP and Mg; this enzyme is FAD-independent and an oligomer of one polypeptide type. The heteromeric biosynthetic acetohydroxyacid-synthase complex is not interchangeable with it.

PMID:25393087

Direct B. subtilis enzyme structure and kinetics establish acetolactate synthesis.

PMID:32855421

The native starting enzyme is explicitly FAD-independent; engineered downstream variants are not native properties.

PMID:7685336

Native alsSD operon regulation links AlsS to post-exponential acetoin production.

Part 2: acetolactate decarboxylation

(S)-2-acetolactate to (R)-acetoin + CO2Reactionaldc_step

Annotons

Acetolactate decarboxylase (AlsD)

aldc_activity

Participant: Family: alpha-acetolactate decarboxylase

Family:

alpha-acetolactate decarboxylasePANTHER:PTHR35524:SF1

Representative Members: alsD (Bacillus subtilis 168)UniProtKB:Q04777

Required Function:

acetolactate decarboxylase activityGO:0047605

Function

acetolactate decarboxylase activityGO:0047605

Substrates: (S)-2-acetolactate

Products: (R)-acetoin CO2

PMID:29796971

Target structure and enzyme characterization support acetolactate decarboxylation.

PMID:7685336

Native alsD genetics links the enzyme to acetoin production.

Part 2: acetoin reduction

(R)-acetoin + NADH to (R,R)-2,3-butanediol + NAD+Reactionbdh_step

Variant set: R,R-butanediol dehydrogenase implementations by functional lineage (One Or More)

Fungal Bdh1Reactionyeast_bdh_variant

Annotons

(R,R)-butanediol dehydrogenase

bdh_activity

Participant: Family: zinc medium-chain polyol dehydrogenase (sorbitol dehydrogenase family)

Family:

zinc medium-chain polyol dehydrogenase (sorbitol dehydrogenase family)

Representative Members: BDH1 (S. cerevisiae)UniProtKB:P39714

Required Function:

(R,R)-butanediol dehydrogenase activityGO:0000721

Function

(R,R)-butanediol dehydrogenase activityGO:0000721

Substrates: (R)-acetoin NADH

Products: (R,R)-butane-2,3-diol NAD(+)

NADH-dependent reduction of R-acetoin yields R,R-butanediol; other substrate stereoisomers can yield different products. Native yeast Bdh1 is NADH-dependent, distinct from engineered NADPH variants. Yeast Bdh1 also reduces diacetyl to acetoin; lack of reverse acetoin oxidation does not contradict that separate reduction.

PMID:10938079

Purified yeast Bdh1 reduces acetoin stereospecifically with NADH.

PMID:19329666

Native NADH specificity is distinguished from engineered NADPH conversion.

PMID:26729717

Direct diacetyl reduction by yeast Bdh1 supports the related acetoin-producing activity.

Bacterial BdhAReactionbacterial_bdh_variant

Annotons

Bacterial R,R-butanediol dehydrogenase

bacterial_bdh_activity

Participant: Family: BdhA-like bacterial R,R-butanediol dehydrogenases

Family:

BdhA-like bacterial R,R-butanediol dehydrogenases The narrower R,R-active bacterial subgroup is supported by target biochemistry. SF26 as a whole contains other substrate specificities; no unverified exact functional-clade identifier is asserted.

Representative Members: bdhA (Bacillus subtilis 168)UniProtKB:O34788

Required Function:

(R,R)-butanediol dehydrogenase activityGO:0000721

Function

(R,R)-butanediol dehydrogenase activityGO:0000721

Substrates: (R)-acetoin NADH

Products: (R,R)-butane-2,3-diol NAD(+)

Native B. subtilis BdhA reduces R-acetoin to R,R-butanediol with NADH and connects the AlsS/AlsD acetoin pathway. Broader PANTHER membership is not taken as a universal substrate-specificity claim.

PMID:18820069

Native B. subtilis bdhA disruption establishes acetoin/butanediol interconversion.

PMID:36781054

Target R,R-BDH structure and enzyme characterization support catalytic zinc and stereochemistry.