Q6UEH5 · AFLF_ASPPU

Function

function

Norsolorinic acid reductase; 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:15006741, PubMed:15094053).
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, the norsolorinic acid reductase aflE may play a role in the conversion of norsolorinic acid (NOR) to averantin (AVN) (PubMed:15006741).
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).

Pathway

Mycotoxin biosynthesis; aflatoxin biosynthesis.

Features

Showing features for binding site, active site, site.

TypeIDPosition(s)Description
Binding site64NADP+ (UniProtKB | ChEBI)
Active site69Proton donor
Site96Lowers pKa of active site Tyr
Binding site143substrate
Binding site173-174NADP+ (UniProtKB | ChEBI)
Binding site199NADP+ (UniProtKB | ChEBI)
Binding site228-238NADP+ (UniProtKB | ChEBI)
Binding site302-310NADP+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Molecular Functionoxidoreductase activity
Biological Processaflatoxin biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Norsolorinic acid reductase B
  • EC number
  • Alternative names
    • Aflatoxin biosynthesis protein F

Gene names

    • Name
      aflF
    • Synonyms
      norB
    • ORF names
      P875_00052992

Organism names

Accessions

  • Primary accession
    Q6UEH5
  • Secondary accessions
    • A0A0F0HZ86

Proteomes

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004241601-382Norsolorinic acid reductase B

Interaction

Protein-protein interaction databases

Structure

Family & Domains

Sequence similarities

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    382
  • Mass (Da)
    42,555
  • Last updated
    2004-07-05 v1
  • Checksum
    B3A915E8A9080605
MSTSAPLLSRYRQLSPAASIRVSPLCLGAMTFGVSDGEMFGECSKEMAFAILDHFYQQGGNFIDTANGYRAGESEMWLGEWMASRKNRDDIVLATKYAAGYRGHEKNRIQVNYGGTGTKSMRLSVDASLQKLQTSYIDLLYVHWWDYTVSIPELMHALNDLVASGKVHYLGISDSPAWVVSKANQYARDHGLRQFVVYQGLWNAAKRDLERDILPMCLDEGMGLCPYGVLNQGRFRTEEGFRDRDQTNNAGGRNIIPLSEHDRSVSRVLDIVATSKGVPLLQVALAYVMQKAPYVFPIVGVRKVDHLTGVEPAVHISLTDEEVNAIENAYEFDPGFPHTFLSGSMFAQGPPKGGYSPDVVWWTKMLGTFDWVEGAKPIRPQP

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY371490
EMBL· GenBank· DDBJ
AAS66007.1
EMBL· GenBank· DDBJ
Genomic DNA
JZEE01000728
EMBL· GenBank· DDBJ
KJK60795.1
EMBL· GenBank· DDBJ
Genomic DNA

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.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp