A0A075TRL5 · PATH_PENEN
- ProteinCytochrome P450 monooxygenase patH
- GenepatH
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids524 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
- 3-methylphenol + O2 + reduced [NADPH--hemoprotein reductase] = 3-hydroxybenzyl alcohol + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
Cofactor
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).
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.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum membrane | |
Molecular Function | heme binding | |
Molecular Function | iron ion binding | |
Molecular Function | monooxygenase activity | |
Molecular Function | oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen | |
Molecular Function | polyketide synthase activity | |
Biological Process | patulin biosynthetic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCytochrome P450 monooxygenase patH
- EC number
- Alternative names
Gene names
Organism names
- Strains
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Penicillium
Accessions
- Primary accessionA0A075TRL5
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Single-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-4 | Cytoplasmic | ||||
Sequence: MEPF | ||||||
Transmembrane | 5-22 | Helical | ||||
Sequence: LLLLLVLLPAIVLVRYAF | ||||||
Topological domain | 23-524 | Lumenal | ||||
Sequence: TYGHRTSTMPIGPPTLPFIGNIHQITKKYTHIKFTEWAAQYGGLYMLKIGNGNMAVITDRRLVKEVLDRKSGIYSHRPHSFVSHDLITKGNHLLVMHYGDQWRTFRRLVHQHLMETMVENHHTKIVNAEAIQLVRDYMIDPEHHMAHPKRYSNSITNSIVFGIRTANREGANMRRLYKLMEEWSEVMETGATPPVDLFPWLKLLPQWLFNNYIDRAKAIGVQMETLYVDILNKVIKRREDGHNNGTFMDKVLDSQEKHNLPWHQLAFIGGVLMEGGSDTSSSLTLAIVQALIQNPDVQRKAHAEIDAVVGHNRSPVWEDFEKLPYINMIIKEGHRWRPILPLCFPHALGEDDWVDGKFLPKGTIVVVNTWGMHMDPSQPDDPAAFIPERFAKHPQLAPDYVPGTWERRDHYGYGVGRRICPGIHLAERNMFLGIAKLLWAFDFQPGEGPIDSDPVTGYHNGFLYCAKDYSCRPVIRNEVIRDTIEREYATATADVFSRFTEG |
Keywords
- Cellular component
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_5007956284 | 1-524 | Cytochrome P450 monooxygenase patH | |||
Sequence: MEPFLLLLLVLLPAIVLVRYAFTYGHRTSTMPIGPPTLPFIGNIHQITKKYTHIKFTEWAAQYGGLYMLKIGNGNMAVITDRRLVKEVLDRKSGIYSHRPHSFVSHDLITKGNHLLVMHYGDQWRTFRRLVHQHLMETMVENHHTKIVNAEAIQLVRDYMIDPEHHMAHPKRYSNSITNSIVFGIRTANREGANMRRLYKLMEEWSEVMETGATPPVDLFPWLKLLPQWLFNNYIDRAKAIGVQMETLYVDILNKVIKRREDGHNNGTFMDKVLDSQEKHNLPWHQLAFIGGVLMEGGSDTSSSLTLAIVQALIQNPDVQRKAHAEIDAVVGHNRSPVWEDFEKLPYINMIIKEGHRWRPILPLCFPHALGEDDWVDGKFLPKGTIVVVNTWGMHMDPSQPDDPAAFIPERFAKHPQLAPDYVPGTWERRDHYGYGVGRRICPGIHLAERNMFLGIAKLLWAFDFQPGEGPIDSDPVTGYHNGFLYCAKDYSCRPVIRNEVIRDTIEREYATATADVFSRFTEG | ||||||
Glycosylation | 266 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
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).
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
Structure
Sequence
- Sequence statusComplete
- Length524
- Mass (Da)60,202
- Last updated2014-10-29 v1
- Checksum96C747028DE5F15C
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
KF899892 EMBL· GenBank· DDBJ | AIG62144.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
JQFZ01000262 EMBL· GenBank· DDBJ | KGO52627.1 EMBL· GenBank· DDBJ | Genomic DNA |