Q4WAZ2 · FMAE_ASPFU

Function

function

Monooxygenase; part of the gene cluster that mediates the biosynthesis of fumagillin, a meroterpenoid that has numerous biological activities including irreversible inhibition of human type 2 methionine aminopeptidase (METAP2) (PubMed:23488861, PubMed:24568283).
Within the pathway, the monooxygenase af470 catalyzes the oxidative cleavage of prefumagillin to yield the final compound of the pathway, fumagillin (PubMed:24568283).
The pathway begins with the conversion of farnesyl pyrophosphate (FPP) to beta-trans-bergamotene by the membrane-bound beta-trans-bergamotene synthase af520. The multifunctional cytochrome P450 monooxygenase af510 then converts beta-trans-bergamotene into 5-keto-demethoxyfumagillol via several oxydation steps. 5-keto-demethoxyfumagillol is then subjected to successive C-6 hydroxylation and O-methylation by the dioxygenase af480 and O-methyltransferase af390-400, respectively, to yield 5-keto-fumagillol, which is then stereoselectively reduced by the keto-reductase af490 to 5R-hydroxy-seco-sesquiterpene. The next step is the polyketide transferase af380-catalyzed transfer of a dodecapentaenoyl group synthesized by the polyketide synthase af370 onto 5R-hydroxy-seco-sesquiterpene which leads to the production of prefumagillin. Finally, oxidative cleavage by the monooxygenase af470 converts prefumagillin to fumagillin (Probable) (PubMed:24568283).

Catalytic activity

Biotechnology

Fumagillin and its derivatives have been intensely studied for their potential use in the treatment of amebiasis, microsporidiosis and rheumatoid arthritis (PubMed:12075057, PubMed:14913169, PubMed:18209961).
They have also interesting antiangiogenic properties by the irreversible inhibition of human type 2 methionine aminopeptidase (METAP2) (PubMed:9177176).

Pathway

Secondary metabolite biosynthesis; terpenoid biosynthesis.

GO annotations

AspectTerm
Molecular Functionmonooxygenase activity
Biological Processfumagillin biosynthetic process
Biological Processterpenoid biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Monooxygenase af470
  • EC number
  • Alternative names
    • Fumagillin biosynthesis antibiotic biosynthesis monooxygenase superfamily monooxygenase
      (Fma-ABM
      )

Gene names

    • Name
      af470
    • Synonyms
      fmaE
    • ORF names
      AFUA_8G00470

Organism names

Accessions

  • Primary accession
    Q4WAZ2

Proteomes

Organism-specific databases

Phenotypes & Variants

Disruption phenotype

Completely abolishes the production of fumagillin but leads to the accumulation of the intermediate prefumagillin (PubMed:24082142, PubMed:24568283).

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004370451-275Monooxygenase af470

Expression

Induction

Expression is controlled by the fumagillin biosynthesis cluster regulator fumR (PubMed:24082142).
Expression is also under the control of the developmental and secondary metabolism regulator veA (PubMed:24116213).

Interaction

Protein-protein interaction databases

Sequence

  • Sequence status
    Complete
  • Length
    275
  • Mass (Da)
    31,023
  • Last updated
    2005-07-05 v1
  • Checksum
    27BEE09D00383001
MDQSMKPLLSPTERPRRHLTASVISFFLPNQFRLSTILCIGALLQTILCAVLPLRYAAVPCVTVLLISVLTTIQECFQPNTNSFMADVIRGRTTAQIPGKDGTHGREPGKGSVVVFHLGIQYNHPLGVFAPHMREISNRFLAMQQDILRRKDELGLLAVQNWRGSERDSGNTTLIKYFFKDVESIHKFAHEPLHKETWTYYNQHHPGHVGIFHETFITKDGGYESMYVNCHPILLGRGEVKVNNRKDGTEEWVGTLVSADTPGLKSFKARLGRDD

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AAHF01000014
EMBL· GenBank· DDBJ
EAL85120.1
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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