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G3XMC6 · AZAJ_ASPNA

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).

Pathway

Secondary metabolite biosynthesis.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site43-48NADP+ (UniProtKB | ChEBI)
Binding site133-140substrate
Binding site170-173NADP+ (UniProtKB | ChEBI)
Binding site193-196NADP+ (UniProtKB | ChEBI)
Binding site211NADP+ (UniProtKB | ChEBI)
Binding site251-252NADP+ (UniProtKB | ChEBI)
Binding site269-273substrate
Binding site336-337NADP+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Molecular Functionnucleotide binding
Molecular Functionoxidoreductase activity, acting on NAD(P)H

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Dehydrogenase azaJ
  • EC number
  • Alternative names
    • Azaphilone biosynthesis cluster protein azaJ

Gene names

    • Name
      azaJ
    • ORF names
      ASPNIDRAFT_43447

Organism names

Accessions

  • Primary accession
    G3XMC6

Proteomes

Organism-specific databases

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004376261-346Dehydrogenase azaJ

Expression

Induction

Expression is under the control of the azaphilone cluster-specific transcription factor azaR (PubMed:22921072).

Interaction

Protein-protein interaction databases

Structure

Family & Domains

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    346
  • Mass (Da)
    36,262
  • Last updated
    2011-12-14 v1
  • MD5 Checksum
    BDC312E9F09E18426BA63A266F10ECE9
MPTNFAAIVPGKNQSLVVQEAPYPTAGENRIVVRVHALAVNAVDYATQMMGETLFPWVTYPLVLGEDIAGEVVAIGPGVTRFKPGDRVVGHAVGTNSNNSAEGAFQQYVVLLENMASPLPHALEYQQAAVVPLAFSTAIVGLFQKDYLGLQIPSLTPTRTGKTLLIWGGATSVGCNAIQLAVAAGYEVITTCSPHNFDLVKSLGATAVFDYKKPSIRDDLREAFRGKTCAGALAIAGVVPQTRNEAAEACLNLVAESEGDKFVALSMPAPPNVPDGVSCKFIFASTVKDNEVSHQLYGYLGEALAHGSFIAAPEAEVVGTGLEAVQGALNALKQGVSAKKLVVTLP

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
ACJE01000001
EMBL· GenBank· DDBJ
EHA28239.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

Disclaimer

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