Essential maintenance is planned to begin on Fri Jan 24 2025. The website may be temporarily unavailable. Please use our fallback: https://wwwdev.ebi.ac.uk/uniprot/front-end/fallback/ in case of any outage.

P0DUR7 · QULF_PENCI

  • Protein
    FMN-dependent alpha-hydroxy acid dehydrogenase qulF
  • Gene
    qulF
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    3/5

Function

function

FMN-dependent alpha-hydroxy acid dehydrogenase; part of the gene cluster that mediates the biosynthesis of quinolactacin A2 (QUL A2), a fungal alkaloid that features a quinolone-gamma-lactam hybrid, which is a potential pharmacophore for the treatment of cancer and Alzheimer's disease (PubMed:32663343).
The quinolone-gamma-lactam hybrid scaffold is synthesized from the combination of L-isoleucine (L-Ile) and the nonproteinogenic amino acid L-kynurenine, followed by quinolone cyclization, oxidative decarboxylation, and lactam formation (PubMed:32663343).
Additionally, the N-methyl group is derived from methionine, which might be catalyzed by an S-adenosylmethionine (SAM)-dependent methyltransferase (PubMed:32663343).
Bioconversion of L-tryptophan to L-kynurenine could be catalyzed by the indoleamine-2,3-dioxygenase (IDO) qulI to produce an unstable product, N-formyl-L-kynurenine, followed by kynurenine formamidase catalyzed hydrolysis (PubMed:32663343).
QulM then acts as a methyltransferase that methylates L-kynurenine at the N-4 position (PubMed:32663343).
The FMN-dependent alpha-hydroxy acid dehydrogenase qulF than functions as an oxidative decarboxylase which converts N-methylkynurenine into 2-aminobenzoylacetamide via 2 tandem reactions, including dehydrogenation and decarboxylation (PubMed:32663343).
An amidase located outside of the qul gene cluster further produces the unstable beta-keto acid precursor N-methyl-2-aminobenzoylacetate, which could be spontaneously dehydrated to form N-methyl-4-hydroxy-2-quinolone (PubMed:32663343).
The NRPS qulB is able to incorporate N-methyl-2-aminobenzoylacetate and efficiently compete with the spontaneous reaction (PubMed:32663343).
By further extending the beta-keto acid with L-Ile, qulA performs a Dieckmann condensation to form the gamma-lactam ring and release a 4-ketopyrrolidinone intermediate from the assembly line (PubMed:32663343).
This intermediate could plausibly further undergo a spontaneous cyclization to yield the final quinolone-gamma-lactam hybrid structure (PubMed:32663343).

Cofactor

FMN (UniProtKB | Rhea| CHEBI:58210 )

Features

Showing features for binding site, active site.

Type
IDPosition(s)Description
Binding site48a 2-oxocarboxylate (UniProtKB | ChEBI)
Binding site130FMN (UniProtKB | ChEBI)
Binding site152FMN (UniProtKB | ChEBI)
Binding site154a 2-oxocarboxylate (UniProtKB | ChEBI)
Binding site189a 2-oxocarboxylate (UniProtKB | ChEBI)
Binding site265FMN (UniProtKB | ChEBI)
Active site289Proton acceptor
Binding site292a 2-oxocarboxylate (UniProtKB | ChEBI)
Binding site320-324FMN (UniProtKB | ChEBI)
Binding site343-344FMN (UniProtKB | ChEBI)

GO annotations

AspectTerm
Molecular FunctionFMN binding
Molecular Functionoxidoreductase activity

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    FMN-dependent alpha-hydroxy acid dehydrogenase qulF
  • EC number
  • Alternative names
    • Quinolactacin A2 biosynthesis cluster protein F

Gene names

    • Name
      qulF

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Penicillium

Accessions

  • Primary accession
    P0DUR7

Phenotypes & Variants

Disruption phenotype

Impairs the production of quinolactacin A2 and leads to the accumulatin of N-methylkynurenine.

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis289Blocks the formatin of 2-aminobenzoylacetamide.

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004534831-402FMN-dependent alpha-hydroxy acid dehydrogenase qulF

Structure

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain22-394FMN hydroxy acid dehydrogenase

Sequence similarities

Belongs to the FMN-dependent alpha-hydroxy acid dehydrogenase family.

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    402
  • Mass (Da)
    44,060
  • Last updated
    2021-09-29 v1
  • MD5 Checksum
    EC5016C8196DA5C61312D8938CCA2CBE
MPPVNFGSYQTKIYHDGTNLNRLPAITTNPTLLEKHAREVLSSRAYSYIAGGAGEKSTMEANRLAFRQWKLVPRVMRPMDDQSISVNLFGQEYKSPLIVGPVGVQGLFHRDKETGVAQVCSELDVPYTLSTASSSSIEDVAAANQAGHRWFQLYWVHDEEILLSLLKRAKENGFTVLVVSLDTWTLGWRPTDLDQGYFPFYAGIGNDVGFSDPVFRAKHEKKGGKIEDDIIGAANAWVSELDDRPHTWEQVEFLRKHWQGPIVLKGIQHADDARRALETGCEGLVVSNHGGRQVDGAIGSLDALPDIVDAVGDKMTVMFDSGVRTGADVIKALCLGAKAVLVGRPVIYGLAIGGKEGAKSVIECLLADLWQGMGLAGMRTVADCNRDCMRRISYPGDLKTML

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.
Help