G3XMC6 · AZAJ_ASPNA
- ProteinDehydrogenase azaJ
- GeneazaJ
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids346 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score2/5
Function
function
Dehydrogenase; part of the gene cluster that mediates the biosynthesis of azaphilones, a class of fungal metabolites characterized by a highly oxygenated pyrano-quinone bicyclic core and exhibiting a broad range of bioactivities (PubMed:22921072).
In the first step, the non-reducing polyketide synthase azaA forms the hexaketide precursor from successive condensations of five malonyl-CoA units, presumably with a simple acetyl-CoA starter unit (PubMed:22921072).
The reactive polyketide chain then undergoes a PT-mediated C2-C7 cyclization to afford the aromatic ring and is eventually released as an aldehyde through the R-domain (PubMed:22921072).
The putative ketoreductase azaE is proposed to catalyze the reduction of the terminal ketone resulting in the early culture product FK17-P2a (PubMed:22921072).
The monooxygenase azaH was demonstrated to be the only enzyme required to convert FK17-P2a to azanigerone E (PubMed:22921072).
AzaH first hydroxylates the benzaldehyde intermediate FK17-P2a at C4, which triggers the formation of the pyran-ring to afford azanigerone E (PubMed:22921072).
In parallel, the 2,4-dimethylhexanoyl chain is synthesized by the HR-PKS azaB and is proposed to be transferred to the C4-hydroxyl of azanigerone E by the acyltransferase azaD directly from the ACP domain of azaB (PubMed:22921072).
Alternatively, the 2,4-dimethyl-hexanoyl chain may be offloaded from the HR-PKS as a carboxylic acid and converted to an acyl-CoA by azaF (PubMed:22921072).
The resulting acyl-CoA molecule could then be taken up as a substrate by AzaD to form azanigerone B (PubMed:22921072).
To yield the carboxylic acid substituent in azanigerone A, the hydroxypropyl side chain of azanigerone B would need to undergo a C-C oxidative cleavage catalyzed by cytochrome P450 AzaI (PubMed:22921072).
AzaI is proposed to act on a vicinal diol that leads to a C-C bond scission either through an alkoxyradical intermediate or a peroxy complex (PubMed:22921072).
In the biosynthesis of azanigerone A, azanigerone B first undergoes hydroxylation at C10, possibly catalyzed by one of the two FAD-dependent monooxygenases encoded in the cluster, azaG or azaL, resulting in the vicinal diol azanigerone C (PubMed:22921072).
Oxidative cleavage of azanigerone C by azaI would yield the corresponding aldehyde derivative of azanigerone A (PubMed:22921072).
Finally, the dehydrogenase azaJ is proposed to convert the aldehyde functional group into the carboxylic acid, completing the conversion from azanigerone B to azanigerone A (PubMed:22921072).
Alternatively, the oxidation of aldehyde to carboxylic acid may be catalyzed by the same P450 enzyme azaI via consecutive oxidation or by endogenous alcohol dehydrogenase (PubMed:22921072).
In the first step, the non-reducing polyketide synthase azaA forms the hexaketide precursor from successive condensations of five malonyl-CoA units, presumably with a simple acetyl-CoA starter unit (PubMed:22921072).
The reactive polyketide chain then undergoes a PT-mediated C2-C7 cyclization to afford the aromatic ring and is eventually released as an aldehyde through the R-domain (PubMed:22921072).
The putative ketoreductase azaE is proposed to catalyze the reduction of the terminal ketone resulting in the early culture product FK17-P2a (PubMed:22921072).
The monooxygenase azaH was demonstrated to be the only enzyme required to convert FK17-P2a to azanigerone E (PubMed:22921072).
AzaH first hydroxylates the benzaldehyde intermediate FK17-P2a at C4, which triggers the formation of the pyran-ring to afford azanigerone E (PubMed:22921072).
In parallel, the 2,4-dimethylhexanoyl chain is synthesized by the HR-PKS azaB and is proposed to be transferred to the C4-hydroxyl of azanigerone E by the acyltransferase azaD directly from the ACP domain of azaB (PubMed:22921072).
Alternatively, the 2,4-dimethyl-hexanoyl chain may be offloaded from the HR-PKS as a carboxylic acid and converted to an acyl-CoA by azaF (PubMed:22921072).
The resulting acyl-CoA molecule could then be taken up as a substrate by AzaD to form azanigerone B (PubMed:22921072).
To yield the carboxylic acid substituent in azanigerone A, the hydroxypropyl side chain of azanigerone B would need to undergo a C-C oxidative cleavage catalyzed by cytochrome P450 AzaI (PubMed:22921072).
AzaI is proposed to act on a vicinal diol that leads to a C-C bond scission either through an alkoxyradical intermediate or a peroxy complex (PubMed:22921072).
In the biosynthesis of azanigerone A, azanigerone B first undergoes hydroxylation at C10, possibly catalyzed by one of the two FAD-dependent monooxygenases encoded in the cluster, azaG or azaL, resulting in the vicinal diol azanigerone C (PubMed:22921072).
Oxidative cleavage of azanigerone C by azaI would yield the corresponding aldehyde derivative of azanigerone A (PubMed:22921072).
Finally, the dehydrogenase azaJ is proposed to convert the aldehyde functional group into the carboxylic acid, completing the conversion from azanigerone B to azanigerone A (PubMed:22921072).
Alternatively, the oxidation of aldehyde to carboxylic acid may be catalyzed by the same P450 enzyme azaI via consecutive oxidation or by endogenous alcohol dehydrogenase (PubMed:22921072).
Pathway
Secondary metabolite biosynthesis.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 43-48 | NADP+ (UniProtKB | ChEBI) | |||
Binding site | 133-140 | substrate | |||
Binding site | 170-173 | NADP+ (UniProtKB | ChEBI) | |||
Binding site | 193-196 | NADP+ (UniProtKB | ChEBI) | |||
Binding site | 211 | NADP+ (UniProtKB | ChEBI) | |||
Binding site | 251-252 | NADP+ (UniProtKB | ChEBI) | |||
Binding site | 269-273 | substrate | |||
Binding site | 336-337 | NADP+ (UniProtKB | ChEBI) | |||
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | nucleotide binding | |
Molecular Function | oxidoreductase activity, acting on NAD(P)H |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDehydrogenase azaJ
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus > Aspergillus subgen. Circumdati
Accessions
- Primary accessionG3XMC6
Proteomes
Organism-specific databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000437626 | 1-346 | Dehydrogenase azaJ | ||
Expression
Induction
Expression is under the control of the azaphilone cluster-specific transcription factor azaR (PubMed:22921072).
Interaction
Protein-protein interaction databases
Structure
Sequence
- Sequence statusComplete
- Length346
- Mass (Da)36,262
- Last updated2011-12-14 v1
- MD5 ChecksumBDC312E9F09E18426BA63A266F10ECE9
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
ACJE01000001 EMBL· GenBank· DDBJ | EHA28239.1 EMBL· GenBank· DDBJ | Genomic DNA |