{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"A0A2I1C3V3","uniProtkbId":"NSRD_ASPN1","entryAudit":{"firstPublicDate":"2021-09-29","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2018-02-28","entryVersion":19,"sequenceVersion":1},"annotationScore":3.0,"organism":{"scientificName":"Aspergillus novofumigatus (strain IBT 16806)","taxonId":1392255,"lineage":["Eukaryota","Fungi","Dikarya","Ascomycota","Pezizomycotina","Eurotiomycetes","Eurotiomycetidae","Eurotiales","Aspergillaceae","Aspergillus","Fumigati"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"30394754"}],"value":"Anthrone oxygenase nsrD"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32105084"}],"value":"1.10.3.-"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"30394754"}],"value":"Neosartorin biosynthesis cluster protein D"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"30394754"}],"value":"nsrD"},"orfNames":[{"value":"P174DRAFT_373009"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30394754"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32105084"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33891392"}],"value":"Anthrone oxygenase; part of the gene cluster that mediates the biosynthesis of the tetrahydroxanthone dimer neosartorin, which exhibits antibacterial activity (PubMed:30394754, PubMed:32105084, PubMed:33891392). The two different monomeric units appear to be synthesized by the same set of enzymes, among which the Baeyer-Villiger monooxygenase nsrF is the key enzyme for the divergence of the biosynthetic routes (PubMed:32105084). The pathway begins with the synthesis of atrochrysone thioester by the polyketide synthase nsrB (PubMed:32105084). The atrochrysone carboxyl ACP thioesterase nsrC then breaks the thioester bond and releases the atrochrysone carboxylic acid from AacuL (PubMed:32105084). Atrochrysone carboxylic acid is decarboxylated by the decarboxylase nsrE, and oxidized by the anthrone oxygenase nsrD to yield emodin (PubMed:32105084). Emodin is then reduced to emodin hydroquinone by the oxidoreductase nsrR (PubMed:32105084). A-ring reduction by the short chain dehydrogenase nsrJ, dehydration by the scytalone dehydratase-like protein nsrI and probable spontaneous re-oxidation, results in overall deoxygenation to chrysophanol (PubMed:32105084). The Baeyer-Villiger monooxygenase nsrF accepts chrysophanol as a substrate to insert one oxygen atom at two different positions to yield the precursors of both monomric units (PubMed:30394754, PubMed:32105084, PubMed:33891392). NsrF is promiscuous/flexible in interacting with the 2 (non methylated and methylated) aromatic rings of chrysophanol, thus diverging the biosynthetic pathway at this point (PubMed:30394754, PubMed:32105084, PubMed:33891392). After the hydrolysis of the lactones, methylesterification by the methyltransferase nsrG yields respectively moniliphenone and 2,2',6'-trihydroxy-4-methyl-6-methoxya-cyldiphenylmethanone (PubMed:30394754, PubMed:32105084). The next steps are the hydroxylation by the FAD-dependent monooxygenase nsrK, followed by isomerization by the monooxygenase nsrQ (PubMed:32105084). The short chain dehydrogenase/reductase nsrO then catalyzes the C-5 ketoreduction to give the xanthone skeleton of blennolide C and 5-acetylblennolide A (PubMed:32105084). The acetyltransferase nsrL has a strict substrate specificity and uses only blennolide A but not blennolide C to yield 5-acetylblennolide A as the single-acetylated product (PubMed:30394754). In the final step of the biosynthesis, the heterodimerization of the 2 xanthones, blennolide C and 5-acetylblennolide A, is catalyzed by the cytochrome P450 monooxygenase nsrP (PubMed:30394754). NsrP can utilize at least three different xanthones as its substrates to perform the dimerization reaction (PubMed:30394754)"}],"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:0000269","source":"PubMed","id":"32105084"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:64269"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32105084"}]}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"30394754"}],"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":162,"modifier":"EXACT"}},"description":"Anthrone oxygenase nsrD","featureId":"PRO_0000453439"},{"type":"Transmembrane","location":{"start":{"value":17,"modifier":"EXACT"},"end":{"value":37,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":54,"modifier":"EXACT"},"end":{"value":74,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":86,"modifier":"EXACT"},"end":{"value":106,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":130,"modifier":"EXACT"},"end":{"value":150,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Glycosylation","location":{"start":{"value":109,"modifier":"EXACT"},"end":{"value":109,"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-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":"29317534","citationType":"journal article","authors":["Kjaerboelling I.","Vesth T.C.","Frisvad J.C.","Nybo J.L.","Theobald S.","Kuo A.","Bowyer P.","Matsuda Y.","Mondo S.","Lyhne E.K.","Kogle M.E.","Clum A.","Lipzen A.","Salamov A.","Ngan C.Y.","Daum C.","Chiniquy J.","Barry K.","LaButti K.","Haridas S.","Simmons B.A.","Magnuson J.K.","Mortensen U.H.","Larsen T.O.","Grigoriev I.V.","Baker S.E.","Andersen M.R."],"citationCrossReferences":[{"database":"PubMed","id":"29317534"},{"database":"DOI","id":"10.1073/pnas.1715954115"}],"title":"Linking secondary metabolites to gene clusters through genome sequencing of six diverse Aspergillus species.","publicationDate":"2018","journal":"Proc. Natl. Acad. Sci. U.S.A.","firstPage":"E753","lastPage":"E761","volume":"115"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"IBT 16806","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"30394754","citationType":"journal article","authors":["Matsuda Y.","Gotfredsen C.H.","Larsen T.O."],"citationCrossReferences":[{"database":"PubMed","id":"30394754"},{"database":"DOI","id":"10.1021/acs.orglett.8b03123"}],"title":"Genetic characterization of neosartorin biosynthesis provides insight into heterodimeric natural product generation.","publicationDate":"2018","journal":"Org. Lett.","firstPage":"7197","lastPage":"7200","volume":"20"},"referencePositions":["FUNCTION"]},{"referenceNumber":3,"citation":{"id":"32105084","citationType":"journal article","authors":["Wei X.","Matsuda Y."],"citationCrossReferences":[{"database":"PubMed","id":"32105084"},{"database":"DOI","id":"10.1021/acs.orglett.0c00285"}],"title":"Unraveling the fungal strategy for tetrahydroxanthone biosynthesis and diversification.","publicationDate":"2020","journal":"Org. Lett.","firstPage":"1919","lastPage":"1923","volume":"22"},"referencePositions":["FUNCTION","CATALYTIC ACTIVITY","PATHWAY"]},{"referenceNumber":4,"citation":{"id":"33891392","citationType":"journal article","authors":["Wei X.","Chen X.","Chen L.","Yan D.","Wang W.G.","Matsuda Y."],"citationCrossReferences":[{"database":"PubMed","id":"33891392"},{"database":"DOI","id":"10.1021/acs.jnatprod.1c00022"}],"title":"Heterologous biosynthesis of tetrahydroxanthone dimers: determination of key factors for selective or divergent synthesis.","publicationDate":"2021","journal":"J. Nat. Prod.","firstPage":"1544","lastPage":"1549","volume":"84"},"referencePositions":["FUNCTION"]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"MSZS01000005","properties":[{"key":"ProteinId","value":"PKX92306.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"AlphaFoldDB","id":"A0A2I1C3V3","properties":[{"key":"Description","value":"-"}]},{"database":"STRING","id":"1392255.A0A2I1C3V3","properties":[{"key":"Description","value":"-"}]},{"database":"GlyCosmos","id":"A0A2I1C3V3","properties":[{"key":"glycosylation","value":"1 site, No reported glycans"}]},{"database":"VEuPathDB","id":"FungiDB:P174DRAFT_373009","properties":[{"key":"Description","value":"-"}]},{"database":"OMA","id":"PFTWVFM","properties":[{"key":"Fingerprint","value":"-"}]},{"database":"OrthoDB","id":"5954308at2759","properties":[{"key":"Description","value":"-"}]},{"database":"Proteomes","id":"UP000234474","properties":[{"key":"Component","value":"Unassembled WGS sequence"}]},{"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":"MTKETYVSATAVVSGSFLSGSMMSLSALVIPLFLDTIDDGPQLLRQWARLYHYGSIYMPALCVATCGIYGYVALSKRAAISPLWSPYVLAAVSTLAMVPFTWWVMVPTNNTLFGLHRSAESTELGVVQVLVVKWAWLHVVRSLYPLFGAFLGFRALIRELRT","length":162,"molWeight":17953,"crc64":"909B54D5D63FB2BB","md5":"67FFF7C518A2A8DEE12C5DAF1F616219"},"extraAttributes":{"countByCommentType":{"FUNCTION":1,"CATALYTIC ACTIVITY":1,"PATHWAY":1,"SUBCELLULAR LOCATION":1,"SIMILARITY":1},"countByFeatureType":{"Chain":1,"Transmembrane":4,"Glycosylation":1},"uniParcId":"UPI000CBBD89F"}}