Q6UEG2 · AFLN_ASPPU

Function

function

Cytochrome P450 monooxygenase; part of the gene cluster that mediates the biosynthesis of aflatoxins, a group of polyketide-derived furanocoumarins, and part of the most toxic and carcinogenic compounds among the known mycotoxins (PubMed:1339261, PubMed:15006741, PubMed:15094053, PubMed:15771506).
The four major aflatoxins produced by A.parasiticus are aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2) (PubMed:15006741).
Within the aflatoxin pathway, with the versicolorin reductase aflM, the cytochrome P450 monooxygenase aflN is involved in conversion of VERA to demethylsterigmatocystin (DMST) (PubMed:1339261, PubMed:15006741, PubMed:15771506).
The biosynthesis of aflatoxins begins with the norsolorinic acid synthase aflC that combines a hexanoyl starter unit produced by the fatty acid synthase aflA/aflB and 7 malonyl-CoA extender units to synthesize the precursor NOR. The second step is the conversion of NOR to averantin and requires the norsolorinic acid ketoreductase aflD, which catalyzes the dehydration of norsolorinic acid to form (1'S)-averantin. The norsolorinic acid reductases aflE and aflF may also play a role in the conversion of NOR to AVN. The cytochrome P450 monooxygenase aflG then catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN). The next step is performed by the 5'-hydroxyaverantin dehydrogenase aflH that transforms HAVN to 5'-oxoaverantin (OAVN) which is further converted to averufin (AVF) by aflK that plays a dual role in the pathway, as a 5'-oxoaverantin cyclase that mediates conversion of 5'-oxoaverantin, as well as a versicolorin B synthase in a later step in the pathway. The averufin oxidase aflI catalyzes the conversion of AVF to versiconal hemiacetal acetate (VHA). VHA is then the substrate for the versiconal hemiacetal acetate esterase aflJ to yield versiconal (VAL). Versicolorin B synthase aflK then converts VAL to versicolorin B (VERB) by closing the bisfuran ring of aflatoxin which is required for DNA-binding, thus giving to aflatoxin its activity as a mutagen. Then, the activity of the versicolorin B desaturase aflL leads to versicolorin A (VERA). A branch point starts from VERB since it can also be converted to dihydrodemethylsterigmatocystin (DMDHST), probably also by aflL, VERA being a precursor for aflatoxins B1 and G1, and DMDHST for aflatoxins B2 and G2. Next, the versicolorin reductase aflM and the cytochrome P450 monooxygenase aflN are involved in conversion of VERA to demethylsterigmatocystin (DMST). AflX and aflY seem also involved in this step, through probable aflX-mediated epoxide ring-opening step following versicolorin A oxidation and aflY-mediated Baeyer-Villiger oxidation required for the formation of the xanthone ring. The methyltransferase aflO then leads to the modification of DMST to sterigmatocystin (ST), and of DMDHST to dihydrosterigmatocystin (DHST). Both ST and DHST are then substrates of the O-methyltransferase aflP to yield O-methylsterigmatocystin (OMST) and dihydro-O-methylsterigmatocystin (DHOMST), respectively. Finally OMST is converted to aflatoxins B1 and G1, and DHOMST to aflatoxins B2 and G2, via the action of several enzymes including O-methylsterigmatocystin oxidoreductase aflQ, the cytochrome P450 monooxygenase aflU, but also the NADH-dependent flavin oxidoreductase nadA which is specifically required for the synthesis of AFG1 (PubMed:15006741).

Cofactor

heme (UniProtKB | Rhea| CHEBI:30413 )

Pathway

Mycotoxin biosynthesis; aflatoxin biosynthesis.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site421Fe (UniProtKB | ChEBI) of heme (UniProtKB | ChEBI); axial binding residue

GO annotations

AspectTerm
Molecular Functionheme binding
Molecular Functioniron ion binding
Molecular Functionmonooxygenase activity
Molecular Functionoxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
Biological Processaflatoxin biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Cytochrome P450 monooxygenase aflN
  • EC number
  • Alternative names
    • Aflatoxin biosynthesis protein N

Gene names

    • Name
      aflN
    • Synonyms
      verA
    • ORF names
      P875_00052981

Organism names

Accessions

  • Primary accession
    Q6UEG2
  • Secondary accessions
    • A0A0F0I292

Proteomes

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004241671-492Cytochrome P450 monooxygenase aflN

Interaction

Protein-protein interaction databases

Structure

Family & Domains

Sequence similarities

Belongs to the cytochrome P450 family.

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    492
  • Mass (Da)
    55,256
  • Last updated
    2004-07-05 v1
  • Checksum
    E2F07168CFF86F54
MPEFSLLAGHFGTLKKTIQGMPSDATLHSIMLKISQQFSSGIFYINMWPFSGTWMVVSTPSAASQIQKLNLTKPVILRRPLETVTGGPSMMSMHGETWKKWRALFNPGFNPGYIIGLAPNITDEVATFWLSCAKGQQGEVFPLESLTTRLTVDSICSVVLDTQLHHQIKDHPLATALQRQIDWTTFGTTFNPLKRYLTIRPLVLWYNNKVMDRIIGGEVDRACRTPPDHPSKSVISLALREYLQEQASTNSTRSLAEFKRLVAPQLRVFLFAGRNTTSSTLIYSYYLLAQHPEVLAKIRAEHEDVLGADPAEAQGRIKEDVQLLNKLPYTTAVIKETLRLFPPSASMREGRPDAEIIGEDGQRYPTVGCNVWTLTVALHHNSDYWDQVENFIPERWLVGPEDPLYPVKGAWRAFEFGPRSCIGQTLAMLELRIALAMTIRQFDITPAYDEWDSIHPATTAKEVNGHRAYQAERGAGGAHTADGFPCRVKERC

Sequence caution

The sequence KJK60752.1 differs from that shown. Reason: Erroneous gene model prediction

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY371490
EMBL· GenBank· DDBJ
AAS66015.1
EMBL· GenBank· DDBJ
Genomic DNA
JZEE01000729
EMBL· GenBank· DDBJ
KJK60752.1
EMBL· GenBank· DDBJ
Genomic DNA Sequence problems.

Similar Proteins

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