ID PATH_PENEN Reviewed; 524 AA. AC A0A075TRL5; DT 05-DEC-2018, integrated into UniProtKB/Swiss-Prot. DT 29-OCT-2014, sequence version 1. DT 16-JAN-2019, entry version 23. DE RecName: Full=Cytochrome P450 monooxygenase patH {ECO:0000303|PubMed:25120234}; DE EC=1.-.-.- {ECO:0000305|PubMed:25120234}; DE AltName: Full=Patulin biosynthesis cluster protein H {ECO:0000303|PubMed:25120234}; DE AltName: Full=m-cresol hydrolase {ECO:0000303|PubMed:25120234}; GN Name=patH {ECO:0000303|PubMed:25120234}; ORFNames=PEX2_082740; OS Penicillium expansum (Blue mold rot fungus). OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes; OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium. OX NCBI_TaxID=27334; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, AND INDUCTION. RC STRAIN=NRRL 35695; RX PubMed=25120234; DOI=10.1016/j.ijfoodmicro.2014.07.028; RA Tannous J., El Khoury R., Snini S.P., Lippi Y., El Khoury A., RA Atoui A., Lteif R., Oswald I.P., Puel O.; RT "Sequencing, physical organization and kinetic expression of the RT patulin biosynthetic gene cluster from Penicillium expansum."; RL Int. J. Food Microbiol. 189C:51-60(2014). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=MD-8; RX PubMed=25338147; DOI=10.1094/MPMI-09-14-0261-FI; RA Ballester A.R., Marcet-Houben M., Levin E., Sela N., Selma-Lazaro C., RA Carmona L., Wisniewski M., Droby S., Gonzalez-Candelas L., RA Gabaldon T.; RT "Genome, transcriptome, and functional analyses of Penicillium RT expansum provide new insights into secondary metabolism and RT pathogenicity."; RL Mol. Plant Microbe Interact. 28:232-248(2015). RN [3] RP BIOTECHNOLOGY. RX PubMed=15082620; DOI=10.1093/ije/dyh028; RG Patulin Clinical Trials Committee, Medical Research Council; RT "Clinical trial of patulin in the common cold. 1944."; RL Int. J. Epidemiol. 33:243-246(2004). RN [4] RP BIOTECHNOLOGY. RX PubMed=22222931; DOI=10.1016/j.fct.2011.12.022; RA de Melo F.T., de Oliveira I.M., Greggio S., Dacosta J.C., RA Guecheva T.N., Saffi J., Henriques J.A., Rosa R.M.; RT "DNA damage in organs of mice treated acutely with patulin, a known RT mycotoxin."; RL Food Chem. Toxicol. 50:3548-3555(2012). RN [5] RP BIOTECHNOLOGY. RX PubMed=26619846; DOI=10.1007/s13277-015-4474-z; RA Boussabbeh M., Ben Salem I., Rjiba-Touati K., Bouyahya C., Neffati F., RA Najjar M.F., Bacha H., Abid-Essefi S.; RT "The potential effect of patulin on mice bearing melanoma cells: an RT anti-tumour or carcinogenic effect?"; RL Tumor Biol. 37:6285-6295(2016). RN [6] RP INDUCTION. RX PubMed=27528575; DOI=10.1111/mpp.12469; RA Kumar D., Barad S., Chen Y., Luo X., Tannous J., Dubey A., RA Glam Matana N., Tian S., Li B., Keller N., Prusky D.; RT "LaeA regulation of secondary metabolism modulates virulence in RT Penicillium expansum and is mediated by sucrose."; RL Mol. Plant Pathol. 18:1150-1163(2017). RN [7] RP FUNCTION, AND INDUCTION. RX PubMed=30100914; DOI=10.3389/fpls.2018.01094; RA Kumar D., Tannous J., Sionov E., Keller N., Prusky D.; RT "Apple intrinsic factors modulating the global regulator, LaeA, the RT patulin gene cluster and patulin accumulation during fruit RT colonization by Penicillium expansum."; RL Front. Plant Sci. 9:1094-1094(2018). CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster CC that mediates the biosynthesis of patulin, an acetate-derived CC tetraketide mycotoxin produced by several fungal species that CC shows antimicrobial properties against several bacteria CC (PubMed:25120234, PubMed:30100914). The pathway begins with the CC synthesis of 6-methylsalicylic acid by the polyketide synthase CC (PKS) patK via condensation of acetate and malonate units. PatG CC then catalyzes the decarboxylation of 6-methylsalicylic acid to CC yield m-cresol. The cytochrome P450 monooxygenase patH then CC converts m-cresol to m-hydroxybenzyl alcohol, which is further CC converted to gentisyl alcohol by the cytochrome P450 monooxygenase CC patI. The conversion of gentisyl alcohol to two-ring compound CC neopatulin remains a matter of speculation, but it involves at CC least two intermediates, isoepoxydon and phyllostin. PatN CC catalyzes the transformation of isoepoxydon into phyllostin. The CC last part of the biosynthetic pathway involves the conversion of CC neopatulin to ascladiol followed by the transformation of the CC latter into patulin (By similarity). CC {ECO:0000250|UniProtKB:A1CFL5, ECO:0000269|PubMed:25120234, CC ECO:0000269|PubMed:30100914}. CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; CC Evidence={ECO:0000250|UniProtKB:P04798}; CC -!- PATHWAY: Mycotoxin biosynthesis; patulin biosynthesis. CC {ECO:0000305|PubMed:25120234}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane CC protein {ECO:0000255}. CC -!- INDUCTION: Expression is correlated with the production of patulin CC (PubMed:25120234). Expression is positively regulated by the CC secondary metabolism regulator laeA (PubMed:27528575, CC PubMed:30100914). Expression is strongly decreased with increased CC sucrose concentrations. This decrease is lost in the presence of CC malic acid (PubMed:30100914). Expression is increased with pH CC changes from 2.5 to 3.5 in the presence of a limiting CC concentration of sucrose, 50 mM (PubMed:30100914). Natural phenols CC present in apple fruits such as chlorogenic acid or the flavonoid CC epicatechin modulate patulin biosynthesis. They increase CC expression in the absence of sucrose, have little impact in the CC presence of 15 mM sucrose, and decrease expression in 175 mM CC sucrose (PubMed:30100914). {ECO:0000269|PubMed:25120234, CC ECO:0000269|PubMed:27528575, ECO:0000269|PubMed:30100914}. CC -!- BIOTECHNOLOGY: Patulin was originally used as an antibiotic and CC specifically trialed to be used against the common cold, but it is CC no longer used for that purpose since it has been shown to induce CC immunological, neurological and gastrointestinal effects CC (PubMed:15082620). Genotoxic effects of patulin with dose- CC dependent increase in DNA strand breaks in brain, liver and CC kidneys have been detected in mice (PubMed:22222931). However, CC more recently, it has been proposed that patulin might also have CC anti-tumor properties (PubMed:26619846). CC {ECO:0000269|PubMed:15082620, ECO:0000269|PubMed:22222931, CC ECO:0000269|PubMed:26619846}. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; KF899892; AIG62144.1; -; Genomic_DNA. DR EMBL; JQFZ01000262; KGO52627.1; -; Genomic_DNA. DR RefSeq; XP_016595357.1; XM_016745544.1. DR EnsemblFungi; KGO43531; KGO43531; PEXP_094320. DR EnsemblFungi; KGO52627; KGO52627; PEX2_082740. DR EnsemblFungi; KGO64340; KGO64340; PEX1_046480. DR GeneID; 27680964; -. DR OrthoDB; 702827at2759; -. DR PhylomeDB; A0A075TRL5; -. DR UniPathway; UPA00918; -. DR Proteomes; UP000030143; Unassembled WGS sequence. DR GO; GO:0020037; F:heme binding; IEA:InterPro. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro. DR Gene3D; 1.10.630.10; -; 1. DR InterPro; IPR001128; Cyt_P450. DR InterPro; IPR002401; Cyt_P450_E_grp-I. DR InterPro; IPR036396; Cyt_P450_sf. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR SUPFAM; SSF48264; SSF48264; 1. PE 1: Evidence at protein level; KW Complete proteome; Glycoprotein; Iron; Membrane; Metal-binding; KW Monooxygenase; Oxidoreductase; Reference proteome; Transmembrane; KW Transmembrane helix. FT CHAIN 1 524 Cytochrome P450 monooxygenase patH. FT /FTId=PRO_5007956284. FT TRANSMEM 4 24 Helical. {ECO:0000255}. FT METAL 442 442 Iron (heme axial ligand). FT {ECO:0000250|UniProtKB:P04798}. FT CARBOHYD 266 266 N-linked (GlcNAc...) asparagine. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. SQ SEQUENCE 524 AA; 60202 MW; 96C747028DE5F15C CRC64; MEPFLLLLLV LLPAIVLVRY AFTYGHRTST MPIGPPTLPF IGNIHQITKK YTHIKFTEWA AQYGGLYMLK IGNGNMAVIT DRRLVKEVLD RKSGIYSHRP HSFVSHDLIT KGNHLLVMHY GDQWRTFRRL VHQHLMETMV ENHHTKIVNA EAIQLVRDYM IDPEHHMAHP KRYSNSITNS IVFGIRTANR EGANMRRLYK LMEEWSEVME TGATPPVDLF PWLKLLPQWL FNNYIDRAKA IGVQMETLYV DILNKVIKRR EDGHNNGTFM DKVLDSQEKH NLPWHQLAFI GGVLMEGGSD TSSSLTLAIV QALIQNPDVQ RKAHAEIDAV VGHNRSPVWE DFEKLPYINM IIKEGHRWRP ILPLCFPHAL GEDDWVDGKF LPKGTIVVVN TWGMHMDPSQ PDDPAAFIPE RFAKHPQLAP DYVPGTWERR DHYGYGVGRR ICPGIHLAER NMFLGIAKLL WAFDFQPGEG PIDSDPVTGY HNGFLYCAKD YSCRPVIRNE VIRDTIEREY ATATADVFSR FTEG //