{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"A0A4P8DK01","uniProtkbId":"DMR16_CRYX8","entryAudit":{"firstPublicDate":"2021-09-29","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2019-07-31","entryVersion":14,"sequenceVersion":1},"annotationScore":3.0,"organism":{"scientificName":"Cryptosporiopsis sp. (strain 8999)","taxonId":2572248,"lineage":["Eukaryota","Fungi","Dikarya","Ascomycota","Pezizomycotina","Leotiomycetes","Helotiales","Dermateaceae","Cryptosporiopsis"]},"proteinExistence":"3: Inferred from homology","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0DOB2"}],"value":"Anthrone oxygenase dmxR16"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0DOB2"}],"value":"1.10.3.-"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"30996871"}],"value":"Dimeric xanthone biosynthesis cluster protein R16"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"30996871"}],"value":"dmxR16"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30996871"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"30996871"}],"value":"Anthrone oxygenase; part of the gene cluster that mediates the biosynthesis of the dimeric xanthones cryptosporioptides (PubMed:30996871). The pathway begins with the synthesis of atrochrysone thioester by the polyketide synthase dmx-nrPKS (Probable). The atrochrysone carboxyl ACP thioesterase dmxR1 then breaks the thioester bond and releases the atrochrysone carboxylic acid from dmx-nrPKS (Probable). Atrochrysone carboxylic acid is decarboxylated by the decarboxylase dmxR15, and oxidized by the anthrone oxygenase dmxR16 to yield emodin (Probable). Emodin is then reduced to emodin hydroquinone by the oxidoreductase dmxR7 (Probable). A-ring reduction by the short chain dehydrogenase dmxR18, dehydration by the scytalone dehydratase-like protein dmxR17 and probable spontaneous re-oxidation, results in overall deoxygenation to chrysophanol (PubMed:30996871). Baeyer-Villiger oxidation by the Baeyer-Villiger monooxygenase (BVMO) dmxR6 then yields monodictylactone in equilibrium with monodictyphenone (PubMed:30996871). In the case of the cryptosporioptides biosynthesis, monodictylactone is reduced at C-12 to an alcohol (by the short chain dehydrogenases dmxR12 or dmxR8) and hydroxylated at C-5 by dmxR9, yielding the electron-rich aromatic which could eliminate H(2)O to form the ortho-quinonemethide, followed by tautomerization to paraquinone and complete the formal reduction to produce the 10-methylgroup (Probable). Conjugate addition of C-4a-OH to the resulting paraquinone by the monooxygenase dmxR10 then gives cyclohexadienone, which is then reduced at C-5 by the short chain dehydrogenase dmxR3 to give the dihydroxanthone (Probable). The 6,7-epoxide in the cryptosporioptides could be introduced by the cytochrome P450 monooxygenase dmxL3 (Probable). The highly reducing PKS dmxL2 manufactures butyrate, which is further carboxylated by dmxL1 to form ethylmalonate (PubMed:30996871). It is not yet clear whether the carboxylation occurs while the butyrate is attached to the ACP of dmxL2, but this unusual fungal metabolite could then be esterified to O-5 by the O-acetyltransferase dmxR13 (PubMed:30996871). Finally, dimerization performed by dmxR5 gives the observed dimers cryptosporioptides A, B and C as the final products of the pathway (PubMed:30996871)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"emodin anthrone + O2 = emodin + H2O + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:64268"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:15379"},{"database":"ChEBI","id":"CHEBI:77659"},{"database":"ChEBI","id":"CHEBI:150013"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0DOB2"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:64269"},"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0DOB2"}]}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"30996871"}],"value":"Secondary metabolite biosynthesis"}],"commentType":"PATHWAY"},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Membrane","id":"SL-0162"},"topology":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Multi-pass membrane protein","id":"SL-9909"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the anthrone oxygenase family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":171,"modifier":"EXACT"}},"description":"Anthrone oxygenase dmxR16","featureId":"PRO_0000453438"},{"type":"Transmembrane","location":{"start":{"value":21,"modifier":"EXACT"},"end":{"value":41,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":67,"modifier":"EXACT"},"end":{"value":87,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":96,"modifier":"EXACT"},"end":{"value":116,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":145,"modifier":"EXACT"},"end":{"value":165,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Glycosylation","location":{"start":{"value":118,"modifier":"EXACT"},"end":{"value":118,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00498"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":129,"modifier":"EXACT"},"end":{"value":129,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00498"}],"featureId":""}],"keywords":[{"id":"KW-0325","category":"PTM","name":"Glycoprotein"},{"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"id":"KW-0503","category":"Molecular function","name":"Monooxygenase"},{"id":"KW-0560","category":"Molecular function","name":"Oxidoreductase"},{"id":"KW-0812","category":"Domain","name":"Transmembrane"},{"id":"KW-1133","category":"Domain","name":"Transmembrane helix"}],"references":[{"referenceNumber":1,"citation":{"id":"30996871","citationType":"journal article","authors":["Greco C.","de Mattos-Shipley K.","Bailey A.M.","Mulholland N.P.","Vincent J.L.","Willis C.L.","Cox R.J.","Simpson T.J."],"citationCrossReferences":[{"database":"PubMed","id":"30996871"},{"database":"DOI","id":"10.1039/c8sc05126g"}],"title":"Structure revision of cryptosporioptides and determination of the genetic basis for dimeric xanthone biosynthesis in fungi.","publicationDate":"2019","journal":"Chem. Sci.","firstPage":"2930","lastPage":"2939","volume":"10"},"referencePositions":["NUCLEOTIDE SEQUENCE [GENOMIC DNA]","FUNCTION","PATHWAY"],"referenceComments":[{"value":"8999","type":"STRAIN"}]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"MK182094","properties":[{"key":"ProteinId","value":"QCL09107.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"AlphaFoldDB","id":"A0A4P8DK01","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"A0A4P8DK01","properties":[{"key":"Description","value":"-"}]},{"database":"GlyCosmos","id":"A0A4P8DK01","properties":[{"key":"glycosylation","value":"2 sites, No reported glycans"}]},{"database":"GO","id":"GO:0016020","properties":[{"key":"GoTerm","value":"C:membrane"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-SubCell"}]},{"database":"InterPro","id":"IPR013901","properties":[{"key":"EntryName","value":"MdpH-2"}]},{"database":"PANTHER","id":"PTHR35042","properties":[{"key":"EntryName","value":"ANTHRONE OXYGENASE ENCC"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR35042:SF3","properties":[{"key":"EntryName","value":"ANTHRONE OXYGENASE-RELATED"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF08592","properties":[{"key":"EntryName","value":"Anthrone_oxy"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"MAPQTKRAAETPKLGVQKAAVIAAAFLSAITAGAMANISMISVPVFMDTNTNPNHMIAQWSRTYHYGHIILPGICVGTCGLYAFSALRSNKNWRRYALAGITTLSLVPFTWVFMTPTNNTLFALEAAGNVSDLGYVQQLVVKWTWLHATRSMFPLIGAILGFTGIMADLER","length":171,"molWeight":18638,"crc64":"EC5EF91ADF628129","md5":"C33D7854B4F15859F6FB07F9C034414B"},"extraAttributes":{"countByCommentType":{"FUNCTION":1,"CATALYTIC ACTIVITY":1,"PATHWAY":1,"SUBCELLULAR LOCATION":1,"SIMILARITY":1},"countByFeatureType":{"Chain":1,"Transmembrane":4,"Glycosylation":2},"uniParcId":"UPI00113C2E21"}}