D-erythroascorbate (dehydro-D-arabinono-1,4-lactone) biosynthesis

In fungi, D-erythroascorbate, the five-carbon analogue of L-ascorbate, is made from D-arabinose in two oxidations. The IUBMB and ChEBI name for it is dehydro-D-arabinono-1,4-lactone. First, a cytosolic aldo-keto-reductase-type D-arabinose 1-dehydrogenase oxidises D-arabinose to D-arabinono-1,4-lactone, using NAD+ or NADP+. Second, a membrane-bound, FAD-dependent D-arabinono-1,4-lactone oxidase in the mitochondria oxidises the lactone with O2, giving dehydro-D-arabinono-1,4-lactone and hydrogen peroxide. The terminal oxidase belongs to the aldonolactone oxidoreductase group of the vanillyl alcohol oxidase flavoprotein superfamily. Its homologs make L-ascorbate in animals (L-gulono-1,4-lactone oxidase) and plants (L-galactono-1,4-lactone dehydrogenase), and the yeast enzyme can also oxidise L-gulono- and L-galactono-1,4-lactone. Erythroascorbate is thought to act as an antioxidant: yeast cells lacking the oxidase are more sensitive to oxidative stress, although its importance under normal conditions is debated.

MODULE:erythroascorbate_biosynthesisDRAFTABSTRACTMetabolic Pathwaymodules/erythroascorbate_biosynthesis.yaml
dehydro-D-arabinono-1,4-lactone biosynthetic processGO:0070485
YeastPathways:PWY3O-6-1
dehydro-D-arabinono-1,4-lactone biosynthesis (S. cerevisiae, SGD YeastPathways)
YeastCyc lists RXN3O-9798 (ARA1, NAD(P)+), RXN3O-9797 (ARA2, NAD+) and 1.1.3.37-RXN (ALO1). All three gene assignments were kept. The two dehydrogenases are modelled as alternative, co-occurring routes into the lactone. ARA2, not ARA1, is the main contributor in vivo (PMID:17097644, PMID:17151466). The YeastCyc and GO-CAM cytosol location for ALO1 was changed to the mitochondrial membrane (PMID:10094636).
GO:0070485
dehydro-D-arabinono-1,4-lactone biosynthetic process
The module is grounded in the GO biological-process term for erythroascorbate biosynthesis.
PMID:10094636
D-Erythroascorbic acid is an important antioxidant molecule in Saccharomyces cerevisiae.
D-arabinono-1,4-lactone oxidase was purified from the mitochondrial fraction and identified as ALO1/YML086C, which has a covalent FAD-binding site and is 32% identical to rat L-gulono-1,4-lactone oxidase. alo1 mutants contain no erythroascorbate and are sensitive to oxidative stress.
PMID:9920381
D-arabinose dehydrogenase and its gene from Saccharomyces cerevisiae.
Cytosolic NADP+-dependent D-arabinose dehydrogenase encoded by YBR149W/ARA1, an aldo-keto reductase. Erythroascorbate was formed in vitro from D-arabinose by this dehydrogenase together with D-arabinono-1,4-lactone oxidase.
PMID:17097644
NAD+-specific D-arabinose dehydrogenase and its contribution to erythroascorbic acid production in Saccharomyces cerevisiae.
YMR041c/ARA2, homologous to plant L-galactose dehydrogenase, is an NAD+-specific D-arabinose dehydrogenase whose Km for D-arabinose is 200-fold lower than that of Ara1p. It is the main source of erythroascorbate made from D-arabinose.
PMID:17151466
NADP(+)-dependent D-arabinose dehydrogenase shows a limited contribution to erythroascorbic acid biosynthesis and oxidative stress resistance in Saccharomyces cerevisiae.
Ara1p is a homodimer, and the earlier "small subunit" is a degradation product. An ara1 mutant still has half its normal erythroascorbate, so Ara1p contributes only a limited share.
PMID:11281285
The biosynthesis of erythroascorbate in Saccharomyces cerevisiae and its role as an antioxidant.
Yeast makes erythroascorbate from D-arabinose or D-arabinono-1,4-lactone. This study found little antioxidant importance for erythroascorbate under the conditions tested.
PMID:26696130
Recent progress on the characterization of aldonolactone oxidoreductases.
Review placing the aldonolactone oxidoreductases (animal GULO, plant GLDH/GULO, fungal ALO) in the flavin-dependent VAO superfamily, where they catalyse the terminal step of ascorbate-type biosynthesis.
5Nodes
2Parts
1Variant Sets
2Variants
3Annotons
1Connections

Derived QC

Recommended-field compliance

40.0% recommended fields populated
  • knowledge_gaps[0] · boundary (0/1)
  • knowledge_gaps[0] · status (0/1)
  • knowledge_gaps[0] · provenance (0/1)

Module deep research

✗ none found

No MODULE:erythroascorbate_biosynthesis 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.

Reaction chaining (advisory)

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

  • arabinose_dehydrogenase_step → arabinonolactone_oxidase_step [NOT_CHECKED]
    Sugar-lactone intermediates; no CoA carrier involved.

Function consistency and core coverage

3 gene-function check(s) reflected in core functions · 0 conflict(s) · 1 evidence or coverage gap(s) (6 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
ara2_dehydrogenase ARA2 (Saccharomyces cerevisiae)
UniProtKB:Q04212
Family Representative 		D-arabinose 1-dehydrogenase (NAD+) activity
GO:0047816 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ara1_dehydrogenase ARA1 (Saccharomyces cerevisiae)
UniProtKB:P38115
Family Representative 		D-arabinose 1-dehydrogenase [NAD(P)+] activity
GO:0045290 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alo1_oxidase ALO1 (Saccharomyces cerevisiae)
UniProtKB:P54783
Family Representative 		D-arabinono-1,4-lactone oxidase activity
GO:0003885 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ara2_dehydrogenase Ara2 / plant L-galactose dehydrogenase-like aldo-keto reductase
PANTHER:PTHR42686
Family 		D-arabinose 1-dehydrogenase (NAD+) activity
GO:0047816 		Family Function Unreviewed
Family review leaves GO:0016491 UNRESOLVED. The narrow PANTHER inventory contains L-galactose, D-arabinose, D-threo-aldose and pyridoxal dehydrogenases, demonstrating substrate divergence within an oxidative AKR-related group. The broad integrated AKR entry also describes reductases and regulatory proteins outside this narrow inventory. CG18547 has AKR and LGALDH-like signatures; these support an oxidoreductase hypothesis without identifying a plant ascorbate pathway or a physiological sugar substrate in fly. A complete set of function-bearing branches is not delimited, so no exhaustive family or subfamily grant is asserted.
ara1_dehydrogenase Ara1 aldo-keto reductase subfamily
PANTHER:PTHR11732:SF503
Family 		D-arabinose 1-dehydrogenase [NAD(P)+] activity
GO:0045290 		Family Supported
Family review supports GO:0045290 for PANTHER:PTHR11732:SF503. ARA1 (SF503), as erythroascorbate_biosynthesis selects.
alo1_oxidase aldonolactone oxidoreductase family (fungal ALO subfamily)
PANTHER:PTHR43762:SF1
Family 		D-arabinono-1,4-lactone oxidase activity
GO:0003885 		Family Supported
Family review supports GO:0003885 for PANTHER:PTHR43762:SF1. Asserted by erythroascorbate_biosynthesis; accepted by ALO1 and alo1.

Gene-review completeness (3/3 grounded genes reviewed)

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

Gene Review Complete Deep research
ALO1 P54783 ✓ ✓ ✓
ARA1 P38115 ✓ 16/17 ✓
ARA2 Q04212 ✓ ✓ ✓

Details

Context
FungiNCBITaxon:4751
D-erythroascorbate biosynthesisMetabolic Pathwayerythroascorbate_biosynthesis
dehydro-D-arabinono-1,4-lactone biosynthetic processGO:0070485
Context
FungiNCBITaxon:4751

Boundary: from free D-arabinose to erythroascorbate. Recycling of oxidised erythroascorbate and its antioxidant reactions are outside the module. Homology and generalisation: PANTHER family PTHR43762 contains S. cerevisiae ALO1 and S. pombe alo1 (SF1, D-arabinono-1,4-lactone oxidase), rat and mouse Gulo (SF8) and Arabidopsis GLDH (SF1). The module therefore names the family, but only the fungal enzyme is a representative member, because the animal and plant homologs make L-ascorbate in different pathways. S. pombe alo1 (UniProtKB:Q9HDX8) has its own gene review; it is not listed as a representative because this group has no PomBase GO-CAM. The ARA1 and ARA2 dehydrogenases are both aldo-keto reductases (UniProt similarity), but PANTHER places them in different families. Naming: the literature calls the product D-erythroascorbic acid, while IUBMB and ChEBI (since 2008) call it dehydro-D-arabinono-1,4-lactone; the GO process term uses the latter.

Connections

D-arabinono-1,4-lactone made in the cytosol is oxidised by the mitochondrial-membrane lactone oxidase.
Part 1: D-arabinose oxidation to the 1,4-lactone
D-arabinose to D-arabinono-1,4-lactoneReactionarabinose_dehydrogenase_step
Variant set: D-arabinose 1-dehydrogenase isozymes by enzyme isoform / nicotinamide cofactor (One Or More)

Both isozymes are present and active in S. cerevisiae. An ara1 ara2 double mutant still contains measurable erythroascorbate (PMID:17097644), so a third enzyme or route may exist.

NAD+-specific D-arabinose dehydrogenase (Ara2-type)Reactionnad_ara2_variant

Annotons

Ara2 NAD+-specific D-arabinose 1-dehydrogenase
ara2_dehydrogenase
Participant: Family: Ara2 / plant L-galactose dehydrogenase-like aldo-keto reductase
Family:
Ara2 / plant L-galactose dehydrogenase-like aldo-keto reductasePANTHER:PTHR42686
Representative Members: ARA2 (Saccharomyces cerevisiae)UniProtKB:Q04212

Function

D-arabinose 1-dehydrogenase (NAD+) activityGO:0047816
Substrates: D-arabinose NAD+
Products: D-arabinono-1,4-lactone NADH

The main dehydrogenase in vivo at physiological (sub-millimolar) D-arabinose concentrations.

NAD(P)+-dependent D-arabinose dehydrogenase (Ara1-type)Reactionnadp_ara1_variant

Annotons

Ara1 NAD(P)+-dependent D-arabinose 1-dehydrogenase
ara1_dehydrogenase
Participant: Family: Ara1 aldo-keto reductase subfamily
Family:
Ara1 aldo-keto reductase subfamilyPANTHER:PTHR11732:SF503
Representative Members: ARA1 (Saccharomyces cerevisiae)UniProtKB:P38115

Function

D-arabinose 1-dehydrogenase [NAD(P)+] activityGO:0045290
Substrates: D-arabinose NADP+ (preferred) or NAD+
Products: D-arabinono-1,4-lactone NAD(P)H

A low-affinity, broad-specificity isozyme (D-arabinose Km in the hundred-millimolar range) with a limited share of erythroascorbate production in vivo.

Part 2: terminal FAD-dependent lactone oxidation
D-arabinono-1,4-lactone to dehydro-D-arabinono-1,4-lactone (erythroascorbate)Reactionarabinonolactone_oxidase_step

Annotons

Alo1 D-arabinono-1,4-lactone oxidase
alo1_oxidase
Participant: Family: aldonolactone oxidoreductase family (fungal ALO subfamily)
Family:
aldonolactone oxidoreductase family (fungal ALO subfamily)
Representative Members: ALO1 (Saccharomyces cerevisiae)UniProtKB:P54783

Function

D-arabinono-1,4-lactone oxidase activityGO:0003885
Substrates: D-arabinono-1,4-lactone O2
Products: dehydro-D-arabinono-1,4-lactone (D-erythroascorbate) hydrogen peroxide

Locations

mitochondrial outer membraneGO:0005741

A covalent-FAD flavoprotein that commits the lactone to erythroascorbate. It is homologous to animal GULO and plant GLDH, the terminal enzymes of L-ascorbate synthesis, and also oxidises L-gulono- and L-galactono-1,4-lactone in vitro.