Protein: FAD-linked oxidoreductase patO (A0A075TR33)
Organism: Penicillium expansum (Blue mold rot fungus)
Function: FAD-linked oxidoreductase; 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. PatO acts with patJ in the vacuole to convert gentisyl alcohol to isoepoxydon. 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)
Subcellular location: Vacuole lumen
Sequence: MRLHQSPPRLLVCILSVLQVSAGLSSNCRCMPGDSCWPSLNDWARFNTSIGGRLVDTQPLGQPCHDPFYTASECNELKQQWTHPELHDASSSSIMSAAVANETCDAFTPRSKPCTLGAMVRYAVNASSPDDFVQTIRFSQERNIRLVIRNTGHDYAGKSTGAGALSIWTHSLKEIDFLNYTSAHYTGPAVRMTAGIQGTDINPAAHKKGLVIVGGECATVGPVGGFTQGGGHSALSSRFGLAADQVLEWEVVDGMGRLLTASPTQNPDLYWALSGGGGGTFGVVYAVTVKTFPDFAVTGVVLQFENIDPSSNRFFEAVGHYHRHLPTYTSAGGMAIAQITNSSFLLTPLTLPAYTAAATKKLLGPFLQDLHQLNISYTLNVTESASYFQHYMKLIEPNPTQLVQNAQYGGRLLPLDLIERNNSQLTDAVQKLTADGVTFVGIGLNVSSSVTGDIWNSVLPGWRTAAMTVILTTSWPLGANLTKMKILADKMTTKWVPILTALSPESGCYMSEADPQQPDWKQTFYGRNYDSLYAIKTKYDPLQTFYATTAVGSEDWQVEAGGRLCQATRKN
InterPro domains: - IPR016166: FAD-binding domain, PCMH-type (domain) [115-294]
- IPR006094: FAD linked oxidase, N-terminal (domain) [122-261]
- IPR050432: FAD-linked Oxidoreductases in Biosynthesis Pathways (family) [56-543]
- IPR036318: FAD-binding, type PCMH-like superfamily (homologous_superfamily) [65-293]
- IPR016169: FAD-binding, type PCMH, subdomain 2 (homologous_superfamily) [86-553]
- IPR012951: Berberine/berberine-like (domain) [508-551]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016491 (oxidoreductase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0019748 (secondary metabolic process), GO:0071704 (organic substance metabolic process), GO:0044281 (small molecule metabolic process), GO:0044550 (secondary metabolite biosynthetic process), GO:1901615 (organic hydroxy compound metabolic process), GO:0006066 (alcohol metabolic process), GO:0044249 (cellular biosynthetic process), GO:0009404 (toxin metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0044283 (small molecule biosynthetic process), GO:0046483 (heterocycle metabolic process), GO:0030638 (polyketide metabolic process), GO:1901334 (lactone metabolic process), GO:1901617 (organic hydroxy compound biosynthetic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0043385 (mycotoxin metabolic process), GO:0009403 (toxin biosynthetic process), GO:0046165 (alcohol biosynthetic process), GO:0018130 (heterocycle biosynthetic process), GO:0030639 (polyketide biosynthetic process), GO:0043386 (mycotoxin biosynthetic process), GO:1901336 (lactone biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0005773 (vacuole), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle)