Q4WAW6 · FTMD_ASPFU

Function

function

6-hydroxytryprostatin B O-methyltransferase; 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: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: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).
In some fungal species, verruculogen is further converted to fumitremorgin A, but the enzymes involved in this step have not been identified yet (Probable)

Caution

In contrast to other A.fumigatus strains, strain ATCC MYA-4609 does not produce indole alkaloids such as fumitremorgins and verruculogen. While the biosynthetic pathway is complete, a variation in this enzyme abolishes production of the tryprostatin A intermediate. The weak methyltransferase activity is probably due to the presence of Leu-202 instead of an Arg residue that affects the binding of 6-hydroxytryprostatin B (PubMed:23649274).

Catalytic activity

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
4.5 μMS-adenosyl-L-methionine
120 μM6-hydroxytryprostatin B
kcat is 8.2 sec-1 with 6-hydroxytryprostatin B as substrate. kcat is 6.9 sec-1 with S-adenosyl-L-methionine as substrate.

Pathway

Mycotoxin biosynthesis.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site201S-adenosyl-L-methionine (UniProtKB | ChEBI)
Active site244Proton acceptor

GO annotations

AspectTerm
Molecular FunctionO-methyltransferase activity
Biological Processfumitremorgin B biosynthetic process
Biological Processmethylation
Biological Processverruculogen biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    6-hydroxytryprostatin B O-methyltransferase
  • EC number
  • Alternative names
    • Fumitremorgin biosynthesis protein D

Gene names

    • Name
      ftmMT
    • Synonyms
      ftmD
    • ORF names
      AFUA_8G00200

Organism names

Accessions

  • Primary accession
    Q4WAW6

Proteomes

Organism-specific databases

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004241281-3426-hydroxytryprostatin B O-methyltransferase

Interaction

Subunit

Homodimer.

Protein-protein interaction databases

Structure

Family & Domains

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    342
  • Mass (Da)
    38,436
  • Last updated
    2005-07-05 v1
  • Checksum
    86BBB3C892654210
MTQAVDIGTIQTLIRLEVPDQVPLTGSIPYDALVKKLKTPVDPELLQRLIRFTRLVGFLDEDAEGAVKHSPMSAIFVNDPDTAGQARFMADFGIRPCSFIYESIKLDPSGEAARQGPLALMAREPGAREGPTFFEVLEKDPVNRKRWHDGMAVHNDSMVRHVAGAYDWGTVQSLVDIGGSEGHVAAVIVNAFPHIQITVQDLPEIIEKARQRGDRHPNIIFEEHDFFTPQPRIADAYFLRLILHDWNDADCTRIVRQISSALRPGARLLIMDAVLPEPGEGSLQSERRLRRSDIGMYTLFSAKERSLAQMRRLVEDCDSRLRFEKLYTPPGSHASMLSWICE

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AAHF01000014
EMBL· GenBank· DDBJ
EAL85146.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
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