{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"W6Q4S2","uniProtkbId":"ORF7_PENRF","entryAudit":{"firstPublicDate":"2020-10-07","lastAnnotationUpdateDate":"2025-02-05","lastSequenceUpdateDate":"2014-04-16","entryVersion":29,"sequenceVersion":1},"annotationScore":2.0,"organism":{"scientificName":"Penicillium roqueforti (strain FM164)","taxonId":1365484,"lineage":["Eukaryota","Fungi","Dikarya","Ascomycota","Pezizomycotina","Eurotiomycetes","Eurotiomycetidae","Eurotiales","Aspergillaceae","Penicillium"]},"proteinExistence":"3: Inferred from homology","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"27921136"}],"value":"PR-toxin biosynthesis cluster protein 7"}}},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"27921136"}],"value":"ORF7"},"orfNames":[{"value":"PROQFM164_S02g001470"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15186158"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16345540"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24239699"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26274339"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27921136"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8440737"}],"value":"Part of the gene cluster that mediates the biosynthesis of PR-toxin, a bicyclic sesquiterpene belonging to the eremophilane class and acting as a mycotoxin (PubMed:24239699, PubMed:27921136). The first step of the pathway is catalyzed by the aristolochene synthase which performs the cyclization of trans,trans-farnesyl diphosphate (FPP) to the bicyclic sesquiterpene aristolochene (PubMed:15186158, PubMed:24239699, PubMed:8440737). Following the formation of aristolochene, the non-oxygenated aristolochene is converted to the trioxygenated intermediate eremofortin B, via 7-epi-neopetasone (PubMed:24239699, PubMed:26274339). This conversion appears to involve three enzymes, a hydroxysterol oxidase-like enzyme, the quinone-oxidase prx3 that forms the quinone-type-structure in the bicyclic nucleus of aristolochene with the C8-oxo group and the C-3 hydroxyl group, and the P450 monooxygenase ORF6 that introduces the epoxide at the double bond between carbons 1 and 2 (PubMed:24239699, PubMed:27921136). No monoxy or dioxy-intermediates have been reported to be released to the broth, so these three early oxidative reactions may be coupled together (PubMed:24239699). Eremofortin B is further oxidized by another P450 monooxygenase, that introduces a second epoxide between carbons 7 and 11 prior to acetylation to eremofortin A by the acetyltransferase ORF8 (PubMed:16345540, PubMed:24239699, PubMed:27921136). The second epoxidation may be performed by a second P450 monooxygenase (PubMed:24239699). After the acetylation step, eremofortin A is converted to eremofortin C and then to PR-toxin (PubMed:24239699). First the conversion of eremofortin A to eremofortin C proceeds by oxidation of the side chain of the molecule at C-12 and is catalyzed by the short-chain oxidoreductase prx1 (PubMed:16345540, PubMed:24239699). The cytochrome P450 monooxygenase ORF6 is probably also involved in this step (PubMed:27921136). The primary alcohol formed at C-12 is finally oxidized by the short-chain alcohol dehydrogenase prx4 that forms PR-toxin (PubMed:16345540, PubMed:24239699)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"24239699"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"27921136"}],"value":"Sesquiterpene biosynthesis"}],"commentType":"PATHWAY"},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Membrane","id":"SL-0162"},"topology":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Single-pass membrane protein","id":"SL-9904"}}]}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":186,"modifier":"EXACT"}},"description":"PR-toxin biosynthesis cluster protein 7","featureId":"PRO_0000451231"},{"type":"Transmembrane","location":{"start":{"value":24,"modifier":"EXACT"},"end":{"value":43,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]}],"keywords":[{"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0812","category":"Domain","name":"Transmembrane"},{"id":"KW-1133","category":"Domain","name":"Transmembrane helix"}],"references":[{"referenceNumber":1,"citation":{"id":"24407037","citationType":"journal article","authors":["Cheeseman K.","Ropars J.","Renault P.","Dupont J.","Gouzy J.","Branca A.","Abraham A.-L.","Ceppi M.","Conseiller E.","Debuchy R.","Malagnac F.","Goarin A.","Silar P.","Lacoste S.","Sallet E.","Bensimon A.","Giraud T.","Brygoo Y."],"citationCrossReferences":[{"database":"PubMed","id":"24407037"},{"database":"DOI","id":"10.1038/ncomms3876"}],"title":"Multiple recent horizontal transfers of a large genomic region in cheese making fungi.","publicationDate":"2014","journal":"Nat. 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