{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"L7WU85","uniProtkbId":"NOTJ_ASPVE","entryAudit":{"firstPublicDate":"2019-12-11","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2013-04-03","entryVersion":23,"sequenceVersion":1},"annotationScore":2.0,"organism":{"scientificName":"Aspergillus versicolor","taxonId":46472,"lineage":["Eukaryota","Fungi","Dikarya","Ascomycota","Pezizomycotina","Eurotiomycetes","Eurotiomycetidae","Eurotiales","Aspergillaceae","Aspergillus","Nidulantes"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"23213353"}],"value":"Notoamide biosynthesis cluster protein J'"}},"flag":"Precursor"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"23213353"}],"value":"notJ'"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22660767"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23213353"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"23213353"}],"value":"Part of the gene cluster that mediates the biosynthesis of notoamide, a fungal indole alkaloid that belongs to a family of natural products containing a characteristic bicyclo[2.2.2]diazaoctane core (PubMed:23213353). The first step of notoamide biosynthesis involves coupling of L-proline and L-tryptophan by the bimodular NRPS notE', to produce cyclo-L-tryptophan-L-proline called brevianamide F (Probable). The reverse prenyltransferase notF' then acts as a deoxybrevianamide E synthase and converts brevianamide F to deoxybrevianamide E via reverse prenylation at C-2 of the indole ring leading to the bicyclo[2.2.2]diazaoctane core (Probable) (PubMed:22660767). Deoxybrevianamide E is further hydroxylated at C-6 of the indole ring, likely catalyzed by the cytochrome P450 monooxygenase notG', to yield 6-hydroxy-deoxybrevianamide E (Probable). 6-hydroxy-deoxybrevianamide E is a specific substrate of the prenyltransferase notC' for normal prenylation at C-7 to produce 6-hydroxy-7-prenyl-deoxybrevianamide, also called notoamide S (Probable). As the proposed pivotal branching point in notoamide biosynthesis, notoamide S can be diverted to notoamide E through an oxidative pyran ring closure putatively catalyzed by either notH' cytochrome P450 monooxygenase or the notD' FAD-linked oxidoreductase (Probable). This step would be followed by an indole 2,3-epoxidation-initiated pinacol-like rearrangement catalyzed by the notB' FAD-dependent monooxygenase leading to the formation of notoamide C and notoamide D (Probable). On the other hand notoamide S is converted to notoamide T by notH' (or notD'), a bifunctional oxidase that also functions as the intramolecular Diels-Alderase responsible for generation of (-)-notoamide T (Probable). To generate antipodal (+)-notoaminide T, notH (or notD) in Aspergillus strain MF297-2 is expected to catalyze a Diels-Alder reaction leading to the opposite stereochemistry (Probable). The remaining oxidoreductase notD' (or notH') likely catalyzes the oxidative pyran ring formation to yield (-)-stephacidin A (Probable). The FAD-dependent monooxygenase notI' is highly similar to notB' and is predicted to catalyze a similar conversion from (-)-stephacidin A to (+)-notoamide B via the 2,3-epoxidation of (-)-stephacidin A followed by a pinacol-type rearrangement (Probable). Finally, it remains unclear which enzyme could be responsible for the final hydroxylation steps leading to notoamide A and sclerotiamide (Probable). The function of notJ' in the notoamide biosynthesis has not been determined yet (Probable)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17304611"}],"value":"Notoamides have been shown to exhibit antitumoral activities (PubMed:17304611). Notoamides A-C show moderate cytotoxicity against HeLa and L1210 cells with IC(50) values in the range of 22-52 mg/ml, but the IC(50) value of notoamide D is greater than 100 mg/ml (PubMed:17304611). Moreover, notoamide C induces G2/M-cell cycle arrest at a concentration of 6.3 mg/ml (PubMed:17304611)"}],"commentType":"BIOTECHNOLOGY"}],"features":[{"type":"Signal","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":22,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Chain","location":{"start":{"value":23,"modifier":"EXACT"},"end":{"value":362,"modifier":"EXACT"}},"description":"Notoamide biosynthesis cluster protein J'","featureId":"PRO_5003985637"},{"type":"Glycosylation","location":{"start":{"value":157,"modifier":"EXACT"},"end":{"value":157,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00498"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":190,"modifier":"EXACT"},"end":{"value":190,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00498"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":280,"modifier":"EXACT"},"end":{"value":280,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00498"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":338,"modifier":"EXACT"},"end":{"value":338,"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-0732","category":"Domain","name":"Signal"}],"references":[{"referenceNumber":1,"citation":{"id":"23213353","citationType":"journal article","authors":["Li S.","Anand K.","Tran H.","Yu F.","Finefield J.M.","Sunderhaus J.D.","McAfoos T.J.","Tsukamoto S.","Williams R.M.","Sherman D.H."],"citationCrossReferences":[{"database":"PubMed","id":"23213353"},{"database":"DOI","id":"10.1039/c2md20029e"}],"title":"Comparative analysis of the biosynthetic systems for fungal bicyclo[2.2.2]diazaoctane indole alkaloids: the (+)/(-)-notoamide, paraherquamide and malbrancheamide pathways.","publicationDate":"2012","journal":"Med. Chem. Commun.","firstPage":"987","lastPage":"996","volume":"3"},"referencePositions":["NUCLEOTIDE SEQUENCE [GENOMIC DNA]"],"referenceComments":[{"value":"NRRL 35600","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"17304611","citationType":"journal article","authors":["Kato H.","Yoshida T.","Tokue T.","Nojiri Y.","Hirota H.","Ohta T.","Williams R.M.","Tsukamoto S."],"citationCrossReferences":[{"database":"PubMed","id":"17304611"},{"database":"DOI","id":"10.1002/anie.200604381"}],"title":"Notoamides A-D: prenylated indole alkaloids isolated from a marine-derived fungus, Aspergillus sp.","publicationDate":"2007","journal":"Angew. Chem. Int. Ed.","firstPage":"2254","lastPage":"2256","volume":"46"},"referencePositions":["BIOTECHNOLOGY"]},{"referenceNumber":3,"citation":{"id":"22660767","citationType":"journal article","authors":["Yin S.","Yu X.","Wang Q.","Liu X.Q.","Li S.M."],"citationCrossReferences":[{"database":"PubMed","id":"22660767"},{"database":"DOI","id":"10.1007/s00253-012-4130-0"}],"title":"Identification of a brevianamide F reverse prenyltransferase BrePT from Aspergillus versicolor with a broad substrate specificity towards tryptophan-containing cyclic dipeptides.","publicationDate":"2013","journal":"Appl. Microbiol. Biotechnol.","firstPage":"1649","lastPage":"1660","volume":"97"},"referencePositions":["FUNCTION"]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"JQ708194","properties":[{"key":"ProteinId","value":"AGC83581.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"AlphaFoldDB","id":"L7WU85","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"L7WU85","properties":[{"key":"Description","value":"-"}]},{"database":"GlyCosmos","id":"L7WU85","properties":[{"key":"glycosylation","value":"4 sites, No reported glycans"}]},{"database":"InterPro","id":"IPR025442","properties":[{"key":"EntryName","value":"DUF4185"}]},{"database":"InterPro","id":"IPR023296","properties":[{"key":"EntryName","value":"Glyco_hydro_beta-prop_sf"}]},{"database":"Pfam","id":"PF13810","properties":[{"key":"EntryName","value":"DUF4185"},{"key":"MatchStatus","value":"1"}]},{"database":"SUPFAM","id":"SSF75005","properties":[{"key":"EntryName","value":"Arabinanase/levansucrase/invertase"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"MRNMATMLHLLTLILLTSPASTQTANAVPKRRLIGEDRESGRRWGVAATDLGIPYDMHNGQVGYLFGDTVSTMWVQEAKDLRSPVMLLSGIHPGEDGGIFFESAAGVDGDGLAPRLFYNGDHGDDGTGTWEFTVLPNDGISFPETGEHIISYTSIMNFTTSWTPNYAGLAYSTDGNSFSRLPTKWLNNDNNTDPFQMWTMQRDGDWVYVFTVRCARQYGPMMLQRVPWDKMTDKTEYQGWGWNGEDWGWQRPCSPILDGYFGEPSVRRLQDGTWAMVYLNASTSTPHIVSRTARGPTGPWSEETVQVNQAGDESLLYGGFIHPWSTGERNQLYLMVSNWTSTSDAAPTPEGLVSVSQFTGTL","length":362,"molWeight":40316,"crc64":"270BCE0806CC9853","md5":"B645258088B180DEA8BE8BF4366261B8"},"extraAttributes":{"countByCommentType":{"FUNCTION":1,"BIOTECHNOLOGY":1},"countByFeatureType":{"Signal":1,"Chain":1,"Glycosylation":4},"uniParcId":"UPI0002AD8EFA"}}