Q0CJ57 · ATE_ASPTN
- ProteinCytochrome P450 monooxygenase atE
- GeneatE
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids467 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score3/5
Function
function
Cytochrome P450 monooxygenase; part of the gene cluster that mediates the biosynthesis of terreic acid, a quinone epoxide inhibitor of Bruton's tyrosine kinase (PubMed:24534845, PubMed:25265334).
The first step of the pathway is the synthesis of 6-methylsalicylic acid (6-MSA) by the 6-methylsalicylic acid synthase atX (PubMed:25265334, PubMed:9003280, PubMed:9438344).
In the biosynthesis of 6-MSA, atX utilizes one acetyl-CoA and three malonyl-CoAs as its substrates and catalyzes a series of programmed reactions including Claisen condensation, dehydration, reduction, and cyclization to yield 6-MSA (PubMed:25265334, PubMed:9003280, PubMed:9438344).
The 6-methylsalicylic acid decarboxylase atA then catalyzes the decarboxylative hydroxylation of 6-MSA to 3-methylcatechol (PubMed:25265334).
The next step is the conversion of 3-methylcatechol to terremutin via several oxidation steps involving the cytochrome P450 monooxygenase atE and probably also the cytochrome P450 monooxygenase atG (PubMed:25265334).
Lastly, atC is required for the oxidation of terremutin to terreic acid (PubMed:25265334).
No function could be assigned to atD yet, although it is involved in the biosynthesis of terreic acid (PubMed:25265334).
The first step of the pathway is the synthesis of 6-methylsalicylic acid (6-MSA) by the 6-methylsalicylic acid synthase atX (PubMed:25265334, PubMed:9003280, PubMed:9438344).
In the biosynthesis of 6-MSA, atX utilizes one acetyl-CoA and three malonyl-CoAs as its substrates and catalyzes a series of programmed reactions including Claisen condensation, dehydration, reduction, and cyclization to yield 6-MSA (PubMed:25265334, PubMed:9003280, PubMed:9438344).
The 6-methylsalicylic acid decarboxylase atA then catalyzes the decarboxylative hydroxylation of 6-MSA to 3-methylcatechol (PubMed:25265334).
The next step is the conversion of 3-methylcatechol to terremutin via several oxidation steps involving the cytochrome P450 monooxygenase atE and probably also the cytochrome P450 monooxygenase atG (PubMed:25265334).
Lastly, atC is required for the oxidation of terremutin to terreic acid (PubMed:25265334).
No function could be assigned to atD yet, although it is involved in the biosynthesis of terreic acid (PubMed:25265334).
Cofactor
Biotechnology
Terreic acid is a metabolite with antibiotic properties (PubMed:23686727).
Terric acid acts also as a selective inhibitor of human Bruton's tyrosine kinase in mast cells and other immune cells (PubMed:10051623).
Terric acid acts also as a selective inhibitor of human Bruton's tyrosine kinase in mast cells and other immune cells (PubMed:10051623).
Pathway
Secondary metabolite biosynthesis.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 387 | Fe (UniProtKB | ChEBI) of heme (UniProtKB | ChEBI); axial binding residue | |||
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | heme binding | |
Molecular Function | iron ion binding | |
Molecular Function | monooxygenase activity | |
Molecular Function | oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCytochrome P450 monooxygenase atE
- 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 accessionQ0CJ57
Proteomes
Organism-specific databases
Phenotypes & Variants
Disruption phenotype
Abolishes the production of terreic acid, but accumulates (2Z,4E)-2-methyl-2,4-hexadienedioic acid, a degradation product of 3-methylcatechol (PubMed:25265334).
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000437639 | 1-467 | Cytochrome P450 monooxygenase atE | ||
Interaction
Protein-protein interaction databases
Structure
Sequence
- Sequence statusComplete
- Length467
- Mass (Da)53,877
- Last updated2006-10-17 v1
- Checksum98F88D661ABD5F3F
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
CH476602 EMBL· GenBank· DDBJ | EAU32821.1 EMBL· GenBank· DDBJ | Genomic DNA |