A1CFL8 · PATK_ASPCL
- Protein6-methylcalicylic acide synthase
- GenepatK
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids1720 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score4/5
Function
function
6-methylsalicylic acid synthase; 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 (By similarity).
PatK catalyzes the first step of the pathway which is the synthesis of 6-methylsalicylic acid via condensation of 1 acetate and 3 malonate units (By similarity).
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:19383676).
PatK catalyzes the first step of the pathway which is the synthesis of 6-methylsalicylic acid via condensation of 1 acetate and 3 malonate units (By similarity).
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:19383676).
Catalytic activity
- 3 malonyl-CoA + acetyl-CoA + NADPH + 3 H+ = 6-methylsalicylate + 3 CO2 + NADP+ + 4 CoA + H2OThis reaction proceeds in the forward direction.
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 active site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Active site | 146 | For beta-ketoacyl synthase activity | |||
Active site | 281 | For beta-ketoacyl synthase activity | |||
Active site | 321 | For beta-ketoacyl synthase activity | |||
Active site | 900 | Proton acceptor; for dehydratase activity | |||
Active site | 1065 | Proton donor; for dehydratase activity | |||
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Molecular Function | 3-oxoacyl-[acyl-carrier-protein] synthase activity | |
Molecular Function | 6-methylsalicylic acid synthase activity | |
Molecular Function | fatty acid synthase activity | |
Molecular Function | phosphopantetheine binding | |
Biological Process | fatty acid biosynthetic process | |
Biological Process | patulin biosynthetic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name6-methylcalicylic acide synthase
- EC number
- Short names6MSAS
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus > Aspergillus subgen. Fumigati
Accessions
- Primary accessionA1CFL8
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000437111 | 1-1720 | 6-methylcalicylic acide synthase | ||
Modified residue | 1678 | O-(pantetheine 4'-phosphoryl)serine | |||
Keywords
- PTM
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Region | 1-31 | Disordered | |||
Domain | 1-399 | Ketosynthase family 3 (KS3) | |||
Compositional bias | 14-29 | Basic and acidic residues | |||
Region | 509-823 | Malonyl-CoA:ACP transacylase (MAT) domain | |||
Region | 868-987 | N-terminal hotdog fold | |||
Region | 868-1139 | Dehydratase (DH) domain | |||
Domain | 868-1144 | PKS/mFAS DH | |||
Region | 1001-1144 | C-terminal hotdog fold | |||
Region | 1148-1545 | Product template (PT) domain | |||
Domain | 1644-1718 | Carrier | |||
Domain
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm (By similarity).
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,720
- Mass (Da)185,005
- Last updated2007-01-23 v1
- Checksum828565A00E61ADB3
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Compositional bias | 14-29 | Basic and acidic residues | |||
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
DS027052 EMBL· GenBank· DDBJ | EAW11667.1 EMBL· GenBank· DDBJ | Genomic DNA |