{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"B0XWK8","uniProtkbId":"HASD_ASPFC","entryAudit":{"firstPublicDate":"2024-11-27","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2008-04-08","entryVersion":91,"sequenceVersion":1},"annotationScore":4.0,"organism":{"scientificName":"Aspergillus fumigatus (strain CBS 144.89 / FGSC A1163 / CEA10)","commonName":"Neosartorya fumigata","taxonId":451804,"lineage":["Eukaryota","Fungi","Dikarya","Ascomycota","Pezizomycotina","Eurotiomycetes","Eurotiomycetidae","Eurotiales","Aspergillaceae","Aspergillus","Fumigati"]},"proteinExistence":"2: Evidence at transcript level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"23360537"}],"value":"Nonribosomal peptide synthetase hasD"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"23360537"}],"value":"6.3.2.-"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"23360537"}],"value":"Hexadehydro-astechrome biosynthesis cluster protein D"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"23360537"}],"value":"hasD"},"orfNames":[{"value":"AFUB_036270"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23360537"}],"value":"Nonribosomal peptide synthetase; part of the gene cluster that mediates the biosynthesis of hexadehydro-astechrome (HAS), a tryptophan-derived iron(III)-complex that acts as a virulence factor in infected mice (PubMed:23360537). Within the pathway, the NRPS condenses tryptophan and alanine to produce the Trp-Ala dipeptide (PubMed:23360537). The 7-dimethylallyltryptophan synthase hasE then catalyzes the prenylation of the hasD-tethered tryptophan or the resulting tethered Trp-Ala dipeptide at the C-7 position of the indole moiety. HAS biosynthesis continues via tethered intermediates with the succesive actions of the cytochrome P450 monooxygenase hasH, the O-methyltransferase hasC, and the FAD-linked oxidoreductase hasG. The resulting O-methylated diketopiperazine is then released from hasD. Finally, three O-methylated diketopiperazine molecules assemble in a trimeric complex with Fe(III) to produce hexadehydro-astechrome (PubMed:23360537)"}],"commentType":"FUNCTION"},{"commentType":"COFACTOR","cofactors":[{"name":"pantetheine 4'-phosphate","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00258"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:47942"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23360537"}],"value":"Secondary metabolite biosynthesis"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36422047"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"39964163"}],"value":"The expression of the hexadehydro-astechrome cluster is induced by glucose (PubMed:36422047). Expression is negatively regulated by the GATA-type transcription factor nsdD (PubMed:39964163)"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"23360537"}],"value":"NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. HasD has the following architecture: A-T-C-A-T-C-T"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23360537"}],"value":"Does not accumulate prenylated tryptophan derivatives"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the NRP synthetase family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":2273,"modifier":"EXACT"}},"description":"Nonribosomal peptide synthetase hasD","featureId":"PRO_0000461228"},{"type":"Domain","location":{"start":{"value":588,"modifier":"EXACT"},"end":{"value":664,"modifier":"EXACT"}},"description":"Carrier 1","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00258"}]},{"type":"Domain","location":{"start":{"value":1634,"modifier":"EXACT"},"end":{"value":1714,"modifier":"EXACT"}},"description":"Carrier 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