A0A075TRL5 · PATH_PENEN

Function

function

Cytochrome P450 monooxygenase; part of the gene cluster that mediates the biosynthesis of patulin, an acetate-derived tetraketide mycotoxin produced by several fungal species that shows antimicrobial properties against several bacteria (PubMed:25625822, PubMed:30100914, PubMed:30680886).
PatH catalyzes the conversion of m-cresol into m-hydroxybenzyl alcohol (PubMed:30680886).
The pathway begins with the synthesis of 6-methylsalicylic acid by the polyketide synthase (PKS) patK via condensation of acetate and malonate units. The 6-methylsalicylic acid decarboxylase patG then catalyzes the decarboxylation of 6-methylsalicylic acid to yield m-cresol (also known as 3-methylphenol). These first reactions occur in the cytosol. The intermediate m-cresol is then transported into the endoplasmic reticulum where the cytochrome P450 monooxygenase patH converts it to m-hydroxybenzyl alcohol, which is further converted to gentisyl alcohol by the cytochrome P450 monooxygenase patI. The oxidoreductases patJ and patO further convert gentisyl alcohol to isoepoxydon in the vacuole. PatN catalyzes then the transformation of isoepoxydon into phyllostine. The cluster protein patF is responsible for the conversion from phyllostine to neopatulin whereas the alcohol dehydrogenase patD converts neopatulin to E-ascladiol. The steps between isoepoxydon and E-ascladiol occur in the cytosol, and E-ascladiol is probably secreted to the extracellular space by one of the cluster-specific transporters patC or patM. Finally, the secreted patulin synthase patE catalyzes the conversion of E-ascladiol to patulin (Probable) (PubMed:30680886).

Catalytic activity

Cofactor

heme (UniProtKB | Rhea| CHEBI:30413 )

Biotechnology

Patulin was originally used as an antibiotic and specifically trialed to be used against the common cold, but it is no longer used for that purpose since it has been shown to induce immunological, neurological and gastrointestinal effects (PubMed:15082620).
Genotoxic effects of patulin with dose-dependent increase in DNA strand breaks in brain, liver and kidneys have been detected in mice (PubMed:22222931).
However, more recently, it has been proposed that patulin might also have anti-tumor properties (PubMed:26619846).

Pathway

Mycotoxin biosynthesis; patulin biosynthesis.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site442Fe (UniProtKB | ChEBI) of heme (UniProtKB | ChEBI); axial binding residue

GO annotations

AspectTerm
Cellular Componentendoplasmic reticulum
Cellular Componentendoplasmic reticulum membrane
Molecular Functionheme binding
Molecular Functioniron ion binding
Molecular Functionmonooxygenase activity
Molecular Functionoxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
Molecular Functionpolyketide synthase activity
Biological Processpatulin biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Cytochrome P450 monooxygenase patH
  • EC number
  • Alternative names
    • Patulin biosynthesis cluster protein H
    • m-cresol hydrolase

Gene names

    • Name
      patH
    • ORF names
      PEX2_082740

Organism names

Accessions

  • Primary accession
    A0A075TRL5

Proteomes

Organism-specific databases

Subcellular Location

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-4Cytoplasmic
Transmembrane5-22Helical
Topological domain23-524Lumenal

Keywords

Phenotypes & Variants

Disruption phenotype

Completely abolishes the production of patulin and leads to the production of a distinct dark-red pigment.

PTM/Processing

Features

Showing features for chain, glycosylation.

TypeIDPosition(s)Description
ChainPRO_50079562841-524Cytochrome P450 monooxygenase patH
Glycosylation266N-linked (GlcNAc...) asparagine

Keywords

PTM databases

Expression

Induction

Expression is correlated with the production of patulin (PubMed:25120234).
Expression is positively regulated by the secondary metabolism regulator laeA (PubMed:27528575, PubMed:30100914).
Expression is strongly decreased with increased sucrose concentrations. This decrease is lost in the presence of malic acid (PubMed:30100914).
Expression is increased with pH changes from 2.5 to 3.5 in the presence of a limiting concentration of sucrose, 50 mM (PubMed:30100914).
Natural phenols present in apple fruits such as chlorogenic acid or the flavonoid epicatechin modulate patulin biosynthesis. They increase expression in the absence of sucrose, have little impact in the presence of 15 mM sucrose, and decrease expression in 175 mM sucrose (PubMed:30100914).
Expression is positively regulated by the patulin cluster-specific transcription factor patL (PubMed:25625822).
Finally, expression is also positively regulated by the velvet family proteins transcription regulators veA, velB, velC, but not vosA (PubMed:30680886).

Interaction

Protein-protein interaction databases

Family & Domains

Sequence similarities

Belongs to the cytochrome P450 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    524
  • Mass (Da)
    60,202
  • Last updated
    2014-10-29 v1
  • Checksum
    96C747028DE5F15C
MEPFLLLLLVLLPAIVLVRYAFTYGHRTSTMPIGPPTLPFIGNIHQITKKYTHIKFTEWAAQYGGLYMLKIGNGNMAVITDRRLVKEVLDRKSGIYSHRPHSFVSHDLITKGNHLLVMHYGDQWRTFRRLVHQHLMETMVENHHTKIVNAEAIQLVRDYMIDPEHHMAHPKRYSNSITNSIVFGIRTANREGANMRRLYKLMEEWSEVMETGATPPVDLFPWLKLLPQWLFNNYIDRAKAIGVQMETLYVDILNKVIKRREDGHNNGTFMDKVLDSQEKHNLPWHQLAFIGGVLMEGGSDTSSSLTLAIVQALIQNPDVQRKAHAEIDAVVGHNRSPVWEDFEKLPYINMIIKEGHRWRPILPLCFPHALGEDDWVDGKFLPKGTIVVVNTWGMHMDPSQPDDPAAFIPERFAKHPQLAPDYVPGTWERRDHYGYGVGRRICPGIHLAERNMFLGIAKLLWAFDFQPGEGPIDSDPVTGYHNGFLYCAKDYSCRPVIRNEVIRDTIEREYATATADVFSRFTEG

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
KF899892
EMBL· GenBank· DDBJ
AIG62144.1
EMBL· GenBank· DDBJ
Genomic DNA
JQFZ01000262
EMBL· GenBank· DDBJ
KGO52627.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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