B9WZX3 · FTMB_ASPFM
- ProteinTryprostatin B synthase
- GeneftmPT1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids464 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score3/5
Function
function
Brevianamide F prenyltransferase; 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:16000710, PubMed:23649274).
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: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).
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: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).
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
- brevianamide F + dimethylallyl diphosphate = diphosphate + tryprostatin B
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
55 μM | brevianamide F | |||||
74 μM | dimethylallyl diphosphate |
Pathway
Mycotoxin biosynthesis.
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 94 | brevianamide F (UniProtKB | ChEBI) | ||||
Sequence: M | ||||||
Binding site | 102 | brevianamide F (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 113 | dimethylallyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Site | 115 | Required for regioselectivity | ||||
Sequence: G | ||||||
Binding site | 201 | dimethylallyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 203 | dimethylallyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 205 | brevianamide F (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 294 | dimethylallyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 296 | dimethylallyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 380 | dimethylallyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 382 | dimethylallyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 446 | dimethylallyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 450 | dimethylallyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: Y |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | prenyltransferase activity | |
Biological Process | verruculogen biosynthetic process |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameTryprostatin B 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 accessionB9WZX3
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000424112 | 1-464 | Tryprostatin B synthase | |||
Sequence: MPPAPPDQKPCHQLQPAPYRALSESILFGSVDEERWWHSTAPILSRLLISSNYDVDVQYKYLSLYRHLVLPALGPYPQRDPETGIIATQWRSGMVLTGLPIEFSNNVARALIRIGVDPVTADSGTAQDPFNTTRPKVYLETAARLLPGVDLTRFYEFETELVITKAEEAVLQANPDLFRSPWKSQILTAMDLQKSGTVLVKAYFYPQPKSAVTGRSTEDLLVNAIRKVDREGRFETQLANLQRYIERRRRGLHVPGVTADKPPATAADKAFDACSFFPHFLSTDLVEPGKSRVKFYASERHVNLQMVEDIWTFGGLRRDPDALRGLELLRHFWADIQMREGYYTMPRGFCELGKSSAGFEAPMMFHFHLDGSQSPFPDPQMYVCVFGMNSRKLVEGLTTFYRRVGWEEMASHYQGNFLANYPDEDFEKAAHLCAYVSFAYKNGGAYVTLYNHSFNPVGDVSFPN |
Structure
Sequence
- Sequence statusComplete
- Length464
- Mass (Da)52,607
- Last updated2009-04-14 v1
- Checksum75B775A0420B6D5B