Q4WAW9 · FTMF_ASPFU
- ProteinVerruculogen synthase
- GeneftmOx1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids291 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score4/5
Function
function
Verruculogen synthase; part of the gene cluster that mediates the biosynthesis of fumitremorgins, indole alkaloids that carry not only intriguing chemical structures, but also interesting biological and pharmacological activities (PubMed:19763315, PubMed:23649274, PubMed:31117657).
The biosynthesis of fumitremorgin-type alkaloids begins by condensation of the two amino acids L-tryptophan and L-proline to brevianamide F, catalyzed by the non-ribosomal peptide synthetase ftmA (PubMed:16755625).
Brevianamide F is then prenylated by the prenyltransferase ftmPT1/ftmB in the presence of dimethylallyl diphosphate, resulting in the formation of tryprostatin B (PubMed:16000710, PubMed:21105662, PubMed:23090579).
The three cytochrome P450 monooxygenases, ftmP450-1/ftmC, ftmP450-2/ftmE and ftmP450-3/FtmG, are responsible for the conversion of tryprostatin B to 6-hydroxytryprostatin B, tryprostatin A to fumitremorgin C and fumitremorgin C to 12,13-dihydroxyfumitremorgin C, respectively (PubMed:19226505).
The putative methyltransferase ftmMT/ftmD is expected for the conversion of 6-hydroxytryprostatin B to tryprostatin A (Probable). FtmPT2/FtmH catalyzes the prenylation of 12,13-dihydroxyfumitre-morgin C in the presence of dimethylallyl diphosphate, resulting in the formation of fumitremorgin B (PubMed:18683158).
Fumitremorgin B is further converted to verruculogen by ftmOx1/ftmF via the insertion of an endoperoxide bond between the two prenyl moieties (PubMed:19763315, PubMed:31117657).
In some fungal species, verruculogen is further converted to fumitremorgin A, but the enzymes involved in this step have not been identified yet (Probable)
The biosynthesis of fumitremorgin-type alkaloids begins by condensation of the two amino acids L-tryptophan and L-proline to brevianamide F, catalyzed by the non-ribosomal peptide synthetase ftmA (PubMed:16755625).
Brevianamide F is then prenylated by the prenyltransferase ftmPT1/ftmB in the presence of dimethylallyl diphosphate, resulting in the formation of tryprostatin B (PubMed:16000710, PubMed:21105662, PubMed:23090579).
The three cytochrome P450 monooxygenases, ftmP450-1/ftmC, ftmP450-2/ftmE and ftmP450-3/FtmG, are responsible for the conversion of tryprostatin B to 6-hydroxytryprostatin B, tryprostatin A to fumitremorgin C and fumitremorgin C to 12,13-dihydroxyfumitremorgin C, respectively (PubMed:19226505).
The putative methyltransferase ftmMT/ftmD is expected for the conversion of 6-hydroxytryprostatin B to tryprostatin A (Probable). FtmPT2/FtmH catalyzes the prenylation of 12,13-dihydroxyfumitre-morgin C in the presence of dimethylallyl diphosphate, resulting in the formation of fumitremorgin B (PubMed:18683158).
Fumitremorgin B is further converted to verruculogen by ftmOx1/ftmF via the insertion of an endoperoxide bond between the two prenyl moieties (PubMed:19763315, PubMed:31117657).
In some fungal species, verruculogen is further converted to fumitremorgin A, but the enzymes involved in this step have not been identified yet (Probable)
Catalytic activity
- fumitremorgin B + AH2 + 2-oxoglutarate + 2 O2 = verruculogen + succinate + A + CO2 + H2O
Cofactor
Pathway
Mycotoxin biosynthesis.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 68 | |||||
Sequence: Y |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | dioxygenase activity | |
Biological Process | verruculogen biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameVerruculogen synthase
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus > Aspergillus subgen. Fumigati
Accessions
- Primary accessionQ4WAW9
Proteomes
Organism-specific databases
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 68 | Affects the catalytic activity. | ||||
Sequence: Y → F |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000424133 | 1-291 | Verruculogen synthase | |||
Sequence: MTVDSKPQLQRLAADADVDRMCRLLEEDGAFILKGLLPFDVVESFNRELDVQMAIPPPKGERLLADKYPPHFKYVPNVATTCPTFRNTVLINPVIHAICEAYFQRTGDYWLSAAFLREIESGMPAQPFHRDDATHPLMHYQPLEAPPVSLSVIFPLTEFTEENGATEVILGSHRWTEVGTPERDQAVLATMDPGDVLIVRQRVVHAGGGNRTTAGKPRRVVLAYFNSVQLTPFETYRTMPREMVESMTVLGQRMLGWRTMKPSDPNIVGINLIDDKRLENVLQLKAADSPA |
Interaction
Subunit
Homodimer.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q4WAW9 | ftmOx1 Q4WAW9 | 3 | EBI-16183015, EBI-16183015 |
Protein-protein interaction databases
Structure
Sequence
- Sequence statusComplete
- Length291
- Mass (Da)32,667
- Last updated2005-07-05 v1
- Checksum7E4E41ABFA1525FD
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AAHF01000014 EMBL· GenBank· DDBJ | EAL85143.1 EMBL· GenBank· DDBJ | Genomic DNA |