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The pathway begins with the synthesis of the backbone drimenol by the terpene cyclase drtB using farnesyl pyrophosphate (FPP) as substrate (PubMed:34468074). The cytochrome P450 monooxygenase drtD is then responsible for the hydroxylations at C-6, C-9 and C-12, as well as the oxidation of hydroxyl groups at C-6 and C-11 to a ketone and an aldehyde, respectively (PubMed:34468074). Then, the biosynthesis can go in two directions, either the hydroxylated drimenol is further hydroxylated at C-2 and C-3 by an enzyme(s) not associated with the drt cluster, or the FAD-binding oxidoreductase drtC further oxidizes C-11 or C-12 to form the butyrolactone ring (PubMed:34468074). DrtB, drtD and drtC are solely responsible for the formation of the different drimane structures observed during drimane sesquiterpenes biosynthesis (PubMed:34468074). The polyketide synthase drtA synthesizes different lengths (C6 and C8) of PKS chains, which are then oxidized to varying degrees by the short-chain dehydrogenase drtF (PubMed:34468074). Finally, these PKS chains are transferred onto drimane sesquiterpenes by the acyltransferase drtE, forming the sesquiterpene esters (PubMed:34468074). 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The polyketide synthase drtA synthesizes different lengths (C6 and C8) of PKS chains, which are then oxidized to varying degrees by the short-chain dehydrogenase drtF (PubMed:34468074). Finally, these PKS chains are transferred onto drimane sesquiterpenes by the acyltransferase drtE, forming the sesquiterpene esters (PubMed:34468074). 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The first step of the pathway is the synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase ausA (PubMed:28233494). 3,5-dimethylorsellinic acid is then prenylated by the polyprenyl transferase ausN (PubMed:28233494). Further epoxidation by the FAD-dependent monooxygenase ausM and cyclization by the probable terpene cyclase ausL lead to the formation of protoaustinoid A (By similarity). Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by the combined action of the FAD-binding monooxygenases ausB and ausC, and the dioxygenase ausE (By similarity). Acid-catalyzed keto-rearrangement and ring contraction of the tetraketide portion of preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (By similarity). The aldo-keto reductase ausK, with the help of ausH, is involved in the next step by transforming preaustinoid A4 into isoaustinone which is in turn hydroxylated by the P450 monooxygenase ausI to form austinolide (By similarity). The cytochrome P450 monooxygenase ausG modifies austinolide to austinol (By similarity). Austinol is further acetylated to austin by the O-acetyltransferase ausP, which spontaneously changes to dehydroaustin (PubMed:28233494). The cytochrome P450 monooxygenase ausR then converts dehydroaustin is into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation catalyzed by ausR permits the O-acetyltransferase ausQ to add an additional acetyl group to the molecule, leading to the formation of acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase ausT catalyzes the reduction of the double bond present between carbon atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an acetylation reaction but also the addition of the PKS ausV diketide product to 1,2-dihydro-7-hydroxydehydroaustin, forming precalidodehydroaustin (PubMed:28233494). Finally, the iron/alpha-ketoglutarate-dependent dioxygenase converts precalidodehydroaustin into calidodehydroaustin (PubMed:28233494)"}],"commentType":"FUNCTION"},{"commentType":"COFACTOR","cofactors":[{"name":"heme","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04798"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:30413"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28233494"}],"value":"Secondary metabolite biosynthesis; terpenoid 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"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28233494"}],"value":"Eesults in loss of 7-hydroxydehydroaustin and accumulates a new product, 1,2-dihydro-dehydroaustin"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"29076725"}],"value":"In A.calidoustus, the austinoid gene cluster lies on a contiguous DNA region, while clusters from E.nidulans and P.brasilianum are split in their respective genomes. Genetic rearrangements provoked variability among the clusters and E.nidulans produces the least number of austionoid derivatives with the end products austinol and dehydroaustinol, while P.brasilianum can produce until acetoxydehydroaustin, and A.calidoustus produces the highest number of identified derivatives"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the cytochrome P450 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":500,"modifier":"EXACT"}},"description":"Cytochrome P450 monooxygenase ausR","featureId":"PRO_0000453842"},{"type":"Transmembrane","location":{"start":{"value":15,"modifier":"EXACT"},"end":{"value":35,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Binding site","location":{"start":{"value":439,"modifier":"EXACT"},"end":{"value":439,"modifier":"EXACT"}},"description":"axial binding residue","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:30413"},{"database":"ChEBI","id":"CHEBI:18248"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04798"}],"ligand":{"name":"heme","id":"ChEBI:CHEBI:30413"},"ligandPart":{"name":"Fe","id":"ChEBI:CHEBI:18248"}}],"keywords":[{"id":"KW-0349","category":"Ligand","name":"Heme"},{"id":"KW-0408","category":"Ligand","name":"Iron"},{"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"id":"KW-0479","category":"Ligand","name":"Metal-binding"},{"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":"26966204","citationType":"journal article","authors":["Horn F.","Linde J.","Mattern D.J.","Walther G.","Guthke R.","Scherlach K.","Martin K.","Brakhage A.A.","Petzke L.","Valiante V."],"citationCrossReferences":[{"database":"PubMed","id":"26966204"},{"database":"DOI","id":"10.1128/genomea.00102-16"}],"title":"Draft genome sequences of fungus Aspergillus calidoustus.","publicationDate":"2016","journal":"Genome Announc.","firstPage":"0","lastPage":"0","volume":"4"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"SF006504","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"28233494","citationType":"journal article","authors":["Valiante V.","Mattern D.J.","Schueffler A.","Horn F.","Walther G.","Scherlach K.","Petzke L.","Dickhaut J.","Guthke R.","Hertweck C.","Nett M.","Thines E.","Brakhage A.A."],"citationCrossReferences":[{"database":"PubMed","id":"28233494"},{"database":"DOI","id":"10.1021/acschembio.7b00003"}],"title":"Discovery of an Extended Austinoid Biosynthetic Pathway in Aspergillus calidoustus.","publicationDate":"2017","journal":"ACS Chem. 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The first step of the pathway is the synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase ausA (PubMed:28233494). 3,5-dimethylorsellinic acid is then prenylated by the polyprenyl transferase ausN (PubMed:28233494). Further epoxidation by the FAD-dependent monooxygenase ausM and cyclization by the probable terpene cyclase ausL lead to the formation of protoaustinoid A (By similarity). Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by the combined action of the FAD-binding monooxygenases ausB and ausC, and the dioxygenase ausE (By similarity). Acid-catalyzed keto-rearrangement and ring contraction of the tetraketide portion of preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (By similarity). The aldo-keto reductase ausK, with the help of ausH, is involved in the next step by transforming preaustinoid A4 into isoaustinone which is in turn hydroxylated by the P450 monooxygenase ausI to form austinolide (By similarity). The cytochrome P450 monooxygenase ausG modifies austinolide to austinol (By similarity). Austinol is further acetylated to austin by the O-acetyltransferase ausP, which spontaneously changes to dehydroaustin (PubMed:28233494). The cytochrome P450 monooxygenase ausR then converts dehydroaustin is into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation catalyzed by ausR permits the O-acetyltransferase ausQ to add an additional acetyl group to the molecule, leading to the formation of acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase ausT catalyzes the reduction of the double bond present between carbon atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an acetylation reaction but also the addition of the PKS ausV diketide product to 1,2-dihydro-7-hydroxydehydroaustin, forming precalidodehydroaustin (PubMed:28233494). 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The first step of the pathway is the synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase ausA (PubMed:28233494). 3,5-dimethylorsellinic acid is then prenylated by the polyprenyl transferase ausN (PubMed:28233494). Further epoxidation by the FAD-dependent monooxygenase ausM and cyclization by the probable terpene cyclase ausL lead to the formation of protoaustinoid A (By similarity). Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by the combined action of the FAD-binding monooxygenases ausB and ausC, and the dioxygenase ausE (By similarity). Acid-catalyzed keto-rearrangement and ring contraction of the tetraketide portion of preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (By similarity). The aldo-keto reductase ausK, with the help of ausH, is involved in the next step by transforming preaustinoid A4 into isoaustinone which is in turn hydroxylated by the P450 monooxygenase ausI to form austinolide (By similarity). The cytochrome P450 monooxygenase ausG modifies austinolide to austinol (By similarity). Austinol is further acetylated to austin by the O-acetyltransferase ausP, which spontaneously changes to dehydroaustin (PubMed:28233494). The cytochrome P450 monooxygenase ausR then converts dehydroaustin is into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation catalyzed by ausR permits the O-acetyltransferase ausQ to add an additional acetyl group to the molecule, leading to the formation of acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase ausT catalyzes the reduction of the double bond present between carbon atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an acetylation reaction but also the addition of the PKS ausV diketide product to 1,2-dihydro-7-hydroxydehydroaustin, forming precalidodehydroaustin (PubMed:28233494). Finally, the iron/alpha-ketoglutarate-dependent dioxygenase converts precalidodehydroaustin into calidodehydroaustin (PubMed:28233494)"}],"commentType":"FUNCTION"},{"commentType":"COFACTOR","cofactors":[{"name":"heme","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04798"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:30413"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"28233494"}],"value":"Secondary metabolite biosynthesis; terpenoid 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"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"29076725"}],"value":"In A.calidoustus, the austinoid gene cluster lies on a contiguous DNA region, while clusters from E.nidulans and P.brasilianum are split in their respective genomes. Genetic rearrangements provoked variability among the clusters and E.nidulans produces the least number of austionoid derivatives with the end products austinol and dehydroaustinol, while P.brasilianum can produce until acetoxydehydroaustin, and A.calidoustus produces the highest number of identified derivatives"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the cytochrome P450 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":529,"modifier":"EXACT"}},"description":"Cytochrome P450 monooxygenase ausG","featureId":"PRO_0000453837"},{"type":"Transmembrane","location":{"start":{"value":31,"modifier":"EXACT"},"end":{"value":51,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Binding site","location":{"start":{"value":470,"modifier":"EXACT"},"end":{"value":470,"modifier":"EXACT"}},"description":"axial binding residue","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:30413"},{"database":"ChEBI","id":"CHEBI:18248"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04798"}],"ligand":{"name":"heme","id":"ChEBI:CHEBI:30413"},"ligandPart":{"name":"Fe","id":"ChEBI:CHEBI:18248"}}],"keywords":[{"id":"KW-0349","category":"Ligand","name":"Heme"},{"id":"KW-0408","category":"Ligand","name":"Iron"},{"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"id":"KW-0479","category":"Ligand","name":"Metal-binding"},{"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":"26966204","citationType":"journal article","authors":["Horn F.","Linde J.","Mattern D.J.","Walther G.","Guthke R.","Scherlach K.","Martin K.","Brakhage A.A.","Petzke L.","Valiante V."],"citationCrossReferences":[{"database":"PubMed","id":"26966204"},{"database":"DOI","id":"10.1128/genomea.00102-16"}],"title":"Draft genome sequences of fungus Aspergillus calidoustus.","publicationDate":"2016","journal":"Genome Announc.","firstPage":"0","lastPage":"0","volume":"4"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"SF006504","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"28233494","citationType":"journal article","authors":["Valiante V.","Mattern D.J.","Schueffler A.","Horn F.","Walther G.","Scherlach K.","Petzke L.","Dickhaut J.","Guthke R.","Hertweck C.","Nett M.","Thines E.","Brakhage A.A."],"citationCrossReferences":[{"database":"PubMed","id":"28233494"},{"database":"DOI","id":"10.1021/acschembio.7b00003"}],"title":"Discovery of an Extended Austinoid Biosynthetic Pathway in Aspergillus calidoustus.","publicationDate":"2017","journal":"ACS Chem. 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The first step of the pathway is the synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase ausA (PubMed:28233494). 3,5-dimethylorsellinic acid is then prenylated by the polyprenyl transferase ausN (PubMed:28233494). Further epoxidation by the FAD-dependent monooxygenase ausM and cyclization by the probable terpene cyclase ausL lead to the formation of protoaustinoid A (By similarity). Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by the combined action of the FAD-binding monooxygenases ausB and ausC, and the dioxygenase ausE (By similarity). Acid-catalyzed keto-rearrangement and ring contraction of the tetraketide portion of preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (By similarity). The aldo-keto reductase ausK, with the help of ausH, is involved in the next step by transforming preaustinoid A4 into isoaustinone which is in turn hydroxylated by the P450 monooxygenase ausI to form austinolide (By similarity). The cytochrome P450 monooxygenase ausG modifies austinolide to austinol (By similarity). Austinol is further acetylated to austin by the O-acetyltransferase ausP, which spontaneously changes to dehydroaustin (PubMed:28233494). The cytochrome P450 monooxygenase ausR then converts dehydroaustin is into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation catalyzed by ausR permits the O-acetyltransferase ausQ to add an additional acetyl group to the molecule, leading to the formation of acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase ausT catalyzes the reduction of the double bond present between carbon atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an acetylation reaction but also the addition of the PKS ausV diketide product to 1,2-dihydro-7-hydroxydehydroaustin, forming precalidodehydroaustin (PubMed:28233494). Finally, the iron/alpha-ketoglutarate-dependent dioxygenase converts precalidodehydroaustin into calidodehydroaustin (PubMed:28233494). AusS is necessary for austinoids production and may play a possible function as a regulator (PubMed:28233494)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28233494"}],"value":"May play a possible function as a regulator"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"28233494"}],"value":"Secondary metabolite biosynthesis; terpenoid biosynthesis"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q5AR31"}],"value":"Homodimer"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28233494"}],"value":"Leads to a complete loss of austinoid production"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"29076725"}],"value":"In A.calidoustus, the austinoid gene cluster lies on a contiguous DNA region, while clusters from E.nidulans and P.brasilianum are split in their respective genomes. Genetic rearrangements provoked variability among the clusters and E.nidulans produces the least number of austionoid derivatives with the end products austinol and dehydroaustinol, while P.brasilianum can produce until acetoxydehydroaustin, and A.calidoustus produces the highest number of identified derivatives"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the trt14 isomerase family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":144,"modifier":"EXACT"}},"description":"Austinoid biosynthesis cluster protein S","featureId":"PRO_0000453835"}],"keywords":[{"id":"KW-1185","category":"Technical term","name":"Reference proteome"}],"references":[{"referenceNumber":1,"citation":{"id":"26966204","citationType":"journal article","authors":["Horn F.","Linde J.","Mattern D.J.","Walther G.","Guthke R.","Scherlach K.","Martin K.","Brakhage A.A.","Petzke L.","Valiante V."],"citationCrossReferences":[{"database":"PubMed","id":"26966204"},{"database":"DOI","id":"10.1128/genomea.00102-16"}],"title":"Draft genome sequences of fungus Aspergillus calidoustus.","publicationDate":"2016","journal":"Genome Announc.","firstPage":"0","lastPage":"0","volume":"4"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"SF006504","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"28233494","citationType":"journal article","authors":["Valiante V.","Mattern D.J.","Schueffler A.","Horn F.","Walther G.","Scherlach K.","Petzke L.","Dickhaut J.","Guthke R.","Hertweck C.","Nett M.","Thines E.","Brakhage A.A."],"citationCrossReferences":[{"database":"PubMed","id":"28233494"},{"database":"DOI","id":"10.1021/acschembio.7b00003"}],"title":"Discovery of an Extended Austinoid Biosynthetic Pathway in Aspergillus calidoustus.","publicationDate":"2017","journal":"ACS Chem. Biol.","firstPage":"1227","lastPage":"1234","volume":"12"},"referencePositions":["FUNCTION","DISRUPTION PHENOTYPE","PATHWAY"]},{"referenceNumber":3,"citation":{"id":"29076725","citationType":"journal article","authors":["Mattern D.J.","Valiante V.","Horn F.","Petzke L.","Brakhage A.A."],"citationCrossReferences":[{"database":"PubMed","id":"29076725"},{"database":"DOI","id":"10.1021/acschembio.7b00814"}],"title":"Rewiring of the austinoid biosynthetic pathway in filamentous fungi.","publicationDate":"2017","journal":"ACS Chem. Biol.","firstPage":"2927","lastPage":"2933","volume":"12"},"referencePositions":["FUNCTION"]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"CDMC01000024","properties":[{"key":"ProteinId","value":"CEL11258.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"AlphaFoldDB","id":"A0A0U5CJU2","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"A0A0U5CJU2","properties":[{"key":"Description","value":"-"}]},{"database":"STRING","id":"454130.A0A0U5CJU2","properties":[{"key":"Description","value":"-"}]},{"database":"OMA","id":"ACFRQFQ","properties":[{"key":"Fingerprint","value":"-"}]},{"database":"OrthoDB","id":"3758478at2759","properties":[{"key":"Description","value":"-"}]},{"database":"UniPathway","id":"UPA00213","properties":[{"key":"RectionId","value":"-"}]},{"database":"Proteomes","id":"UP000054771","properties":[{"key":"Component","value":"Unassembled WGS sequence"}]},{"database":"GO","id":"GO:0016114","properties":[{"key":"GoTerm","value":"P:terpenoid biosynthetic process"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-UniPathway"}]},{"database":"InterPro","id":"IPR050977","properties":[{"key":"EntryName","value":"Fungal_Meroterpenoid_Isomerase"}]},{"database":"PANTHER","id":"PTHR39598:SF1","properties":[{"key":"EntryName","value":"AUSTINOID BIOSYNTHESIS CLUSTERS PROTEIN F-RELATED"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR39598","properties":[{"key":"EntryName","value":"AUSTINOL SYNTHESIS PROTEIN F-RELATED"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"MSIRERLLATVSRYIAAYNEFDPSAMKTVRTVSCLTHGIAPTCKFTQSVEEHTKHMMLSRGVFRSVNASIVDDGTTVVDEGSRKVVVKVKLRCETIVGPYENEAMFIMAMDEEGTLVDGIFQFLDTACFRQFQGRLEEAHVSRD","length":144,"molWeight":16203,"crc64":"69F2859EFBC92A0C","md5":"0B718EF1556BEA92679E42B19951C87D"},"extraAttributes":{"countByCommentType":{"FUNCTION":2,"PATHWAY":1,"SUBUNIT":1,"DISRUPTION PHENOTYPE":1,"MISCELLANEOUS":1,"SIMILARITY":1},"countByFeatureType":{"Chain":1},"uniParcId":"UPI00073BCC2A"}},{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"A0A0U5CNN8","uniProtkbId":"DRTE_ASPCI","entryAudit":{"firstPublicDate":"2022-02-23","lastAnnotationUpdateDate":"2026-11-04","lastSequenceUpdateDate":"2016-03-16","entryVersion":31,"sequenceVersion":1},"annotationScore":3.0,"organism":{"scientificName":"Aspergillus calidoustus","taxonId":454130,"lineage":["Eukaryota","Fungi","Dikarya","Ascomycota","Pezizomycotina","Eurotiomycetes","Eurotiomycetidae","Eurotiales","Aspergillaceae","Aspergillus","Aspergillus subgen. Nidulantes"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"34468074"}],"value":"Acyltransferase drtE"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}],"value":"2.3.-.-"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"34468074"}],"value":"Drimane-type sesquiterpene ester biosynthesis cluster protein E"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Polyketide transferase drtE"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"34468074"}],"value":"drtE"},"orfNames":[{"value":"ASPCAL02981"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}],"value":"Acyltransferase; part of the gene cluster that mediates the biosynthesis of various drimane-type sesquiterpene esters, compounds that exhibit diverse biological activities and are widely present in eukaryotes (PubMed:34468074). The pathway begins with the synthesis of the backbone drimenol by the terpene cyclase drtB using farnesyl pyrophosphate (FPP) as substrate (PubMed:34468074). The cytochrome P450 monooxygenase drtD is then responsible for the hydroxylations at C-6, C-9 and C-12, as well as the oxidation of hydroxyl groups at C-6 and C-11 to a ketone and an aldehyde, respectively (PubMed:34468074). Then, the biosynthesis can go in two directions, either the hydroxylated drimenol is further hydroxylated at C-2 and C-3 by an enzyme(s) not associated with the drt cluster, or the FAD-binding oxidoreductase drtC further oxidizes C-11 or C-12 to form the butyrolactone ring (PubMed:34468074). DrtB, drtD and drtC are solely responsible for the formation of the different drimane structures observed during drimane sesquiterpenes biosynthesis (PubMed:34468074). The polyketide synthase drtA synthesizes different lengths (C6 and C8) of PKS chains, which are then oxidized to varying degrees by the short-chain dehydrogenase drtF (PubMed:34468074). Finally, these PKS chains are transferred onto drimane sesquiterpenes by the acyltransferase drtE, forming the sesquiterpene esters (PubMed:34468074). In addition to the different fatty acyl-CoA chains produced by drtA, drtE is also able to use cinnamoyl-CoA as a substrate (PubMed:34468074)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}],"value":"Secondary metabolite biosynthesis; terpenoid biosynthesis"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}],"value":"Abolishes the production of all the sesquiterpene ester compounds"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}],"value":"The various drimane-type sesquiterpene esters produced by the A.calidoustus drt cluster include asperiene C, asperiene A, (6-Strobilactone-B) ester of (E,E)-6-carbonyl-7-hydroxy-2,4-octadienoic acid, ustusolate A, ustusolate C, ustusolide E, ustusoic acid A, (2'E,4'E)-6-(1'-carboxyhexa-2',4',-diene)-9-hydroxy-drim-7-ene-11,12-olide, RES-1149-2, as well as the 3 newly identified compounds calidoustene A, calidoustene B and calidoustene C"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the polyketide transferase af380 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":308,"modifier":"EXACT"}},"description":"Acyltransferase drtE","featureId":"PRO_0000454534"},{"type":"Domain","location":{"start":{"value":35,"modifier":"EXACT"},"end":{"value":159,"modifier":"EXACT"}},"description":"AB hydrolase-1","evidences":[{"evidenceCode":"ECO:0000255"}]}],"keywords":[{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0808","category":"Molecular function","name":"Transferase"}],"references":[{"referenceNumber":1,"citation":{"id":"26966204","citationType":"journal article","authors":["Horn F.","Linde J.","Mattern D.J.","Walther G.","Guthke R.","Scherlach K.","Martin K.","Brakhage A.A.","Petzke L.","Valiante V."],"citationCrossReferences":[{"database":"PubMed","id":"26966204"},{"database":"DOI","id":"10.1128/genomea.00102-16"}],"title":"Draft genome sequences of fungus Aspergillus calidoustus.","publicationDate":"2016","journal":"Genome Announc.","firstPage":"0","lastPage":"0","volume":"4"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"SF006504","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"34468074","citationType":"journal article","authors":["Huang Y.","Hoefgen S.","Valiante V."],"citationCrossReferences":[{"database":"PubMed","id":"34468074"},{"database":"DOI","id":"10.1002/anie.202108970"}],"title":"Biosynthesis of fungal drimane-type sesquiterpene esters.","publicationDate":"2021","journal":"Angew. Chem. Int. Ed.","firstPage":"23763","lastPage":"23770","volume":"60"},"referencePositions":["FUNCTION","DISRUPTION PHENOTYPE","CATALYTIC ACTIVITY","PATHWAY"]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"CDMC01000002","properties":[{"key":"ProteinId","value":"CEN60545.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"AlphaFoldDB","id":"A0A0U5CNN8","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"A0A0U5CNN8","properties":[{"key":"Description","value":"-"}]},{"database":"STRING","id":"454130.A0A0U5CNN8","properties":[{"key":"Description","value":"-"}]},{"database":"ESTHER","id":"9euro-a0a0u5cnn8","properties":[{"key":"FamilyName","value":"Thiohydrolase"}]},{"database":"OMA","id":"AAPNYRN","properties":[{"key":"Fingerprint","value":"-"}]},{"database":"OrthoDB","id":"2498029at2759","properties":[{"key":"Description","value":"-"}]},{"database":"UniPathway","id":"UPA00213","properties":[{"key":"RectionId","value":"-"}]},{"database":"Proteomes","id":"UP000054771","properties":[{"key":"Component","value":"Unassembled WGS sequence"}]},{"database":"GO","id":"GO:0016114","properties":[{"key":"GoTerm","value":"P:terpenoid biosynthetic process"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-UniPathway"}]},{"database":"Gene3D","id":"1.10.10.800","properties":[{"key":"EntryName","value":"-"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"3.40.50.1820","properties":[{"key":"EntryName","value":"alpha/beta hydrolase"},{"key":"MatchStatus","value":"1"}]},{"database":"InterPro","id":"IPR000073","properties":[{"key":"EntryName","value":"AB_hydrolase_1"}]},{"database":"InterPro","id":"IPR029058","properties":[{"key":"EntryName","value":"AB_hydrolase_fold"}]},{"database":"InterPro","id":"IPR051411","properties":[{"key":"EntryName","value":"Polyketide_trans_af380-like"}]},{"database":"PANTHER","id":"PTHR47751:SF2","properties":[{"key":"EntryName","value":"DLTD N-TERMINAL DOMAIN PROTEIN (AFU_ORTHOLOGUE AFUA_8G00380)-RELATED"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR47751","properties":[{"key":"EntryName","value":"SUPERFAMILY HYDROLASE, PUTATIVE (AFU_ORTHOLOGUE AFUA_2G16580)-RELATED"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF00561","properties":[{"key":"EntryName","value":"Abhydrolase_1"},{"key":"MatchStatus","value":"1"}]},{"database":"SUPFAM","id":"SSF53474","properties":[{"key":"EntryName","value":"alpha/beta-Hydrolases"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"MSFAFSKVEFEEVEFQTLDKLTLKARLYSAAKRGPALVMNPGYNCTKEISAPSAAAYFQSKGITCLIYDPRNCGQSDGTPRREIDPHRQVDDYLDAMTYMSGLDIVDPDQIGFWGVSFSASIALAAACYDPRAKCIITVSPWTFDFGITAAEAKDNFSRLVAEREAQALGNEPFYTAMVDEEGNNPIHVNVDWGDEVRAAVNEFVSLSADGFVPTVTFQSYYKLFTFSPYLSLKFLGDTPLMMVVPEHDTVCPVEQQVKLYDAVEGPKEIYHAEGKRHLNMLAEDKFFEPMMKPQVEFFFKVMRGEAI","length":308,"molWeight":34562,"crc64":"54CBD533B6AB9A6E","md5":"843E663FF171DD66AFC7CF9111EF3E7C"},"extraAttributes":{"countByCommentType":{"FUNCTION":1,"PATHWAY":1,"DISRUPTION PHENOTYPE":1,"MISCELLANEOUS":1,"SIMILARITY":1},"countByFeatureType":{"Chain":1,"Domain":1},"uniParcId":"UPI00073C50E5"}},{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"A0A0U5GHG9","uniProtkbId":"AUSE_ASPCI","entryAudit":{"firstPublicDate":"2021-09-29","lastAnnotationUpdateDate":"2026-11-04","lastSequenceUpdateDate":"2016-03-16","entryVersion":25,"sequenceVersion":1},"annotationScore":3.0,"organism":{"scientificName":"Aspergillus calidoustus","taxonId":454130,"lineage":["Eukaryota","Fungi","Dikarya","Ascomycota","Pezizomycotina","Eurotiomycetes","Eurotiomycetidae","Eurotiales","Aspergillaceae","Aspergillus","Aspergillus subgen. 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The first step of the pathway is the synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase ausA (PubMed:28233494). 3,5-dimethylorsellinic acid is then prenylated by the polyprenyl transferase ausN (PubMed:28233494). Further epoxidation by the FAD-dependent monooxygenase ausM and cyclization by the probable terpene cyclase ausL lead to the formation of protoaustinoid A (By similarity). Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by the combined action of the FAD-binding monooxygenases ausB and ausC, and the dioxygenase ausE (By similarity). Acid-catalyzed keto-rearrangement and ring contraction of the tetraketide portion of preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (By similarity). The aldo-keto reductase ausK, with the help of ausH, is involved in the next step by transforming preaustinoid A4 into isoaustinone which is in turn hydroxylated by the P450 monooxygenase ausI to form austinolide (By similarity). The cytochrome P450 monooxygenase ausG modifies austinolide to austinol (By similarity). Austinol is further acetylated to austin by the O-acetyltransferase ausP, which spontaneously changes to dehydroaustin (PubMed:28233494). The cytochrome P450 monooxygenase ausR then converts dehydroaustin is into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation catalyzed by ausR permits the O-acetyltransferase ausQ to add an additional acetyl group to the molecule, leading to the formation of acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase ausT catalyzes the reduction of the double bond present between carbon atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an acetylation reaction but also the addition of the PKS ausV diketide product to 1,2-dihydro-7-hydroxydehydroaustin, forming precalidodehydroaustin (PubMed:28233494). 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The cytochrome P450 monooxygenase ausG modifies austinolide to austinol (By similarity). Austinol is further acetylated to austin by the O-acetyltransferase ausP, which spontaneously changes to dehydroaustin (PubMed:28233494). The cytochrome P450 monooxygenase ausR then converts dehydroaustin is into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation catalyzed by ausR permits the O-acetyltransferase ausQ to add an additional acetyl group to the molecule, leading to the formation of acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase ausT catalyzes the reduction of the double bond present between carbon atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an acetylation reaction but also the addition of the PKS ausV diketide product to 1,2-dihydro-7-hydroxydehydroaustin, forming precalidodehydroaustin (PubMed:28233494). 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The first step of the pathway is the synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase ausA (PubMed:28233494). 3,5-dimethylorsellinic acid is then prenylated by the polyprenyl transferase ausN (PubMed:28233494). Further epoxidation by the FAD-dependent monooxygenase ausM and cyclization by the probable terpene cyclase ausL lead to the formation of protoaustinoid A (By similarity). Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by the combined action of the FAD-binding monooxygenases ausB and ausC, and the dioxygenase ausE (By similarity). Acid-catalyzed keto-rearrangement and ring contraction of the tetraketide portion of preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (By similarity). The aldo-keto reductase ausK, with the help of ausH, is involved in the next step by transforming preaustinoid A4 into isoaustinone which is in turn hydroxylated by the P450 monooxygenase ausI to form austinolide (By similarity). The cytochrome P450 monooxygenase ausG modifies austinolide to austinol (By similarity). Austinol is further acetylated to austin by the O-acetyltransferase ausP, which spontaneously changes to dehydroaustin (PubMed:28233494). The cytochrome P450 monooxygenase ausR then converts dehydroaustin is into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation catalyzed by ausR permits the O-acetyltransferase ausQ to add an additional acetyl group to the molecule, leading to the formation of acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase ausT catalyzes the reduction of the double bond present between carbon atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an acetylation reaction but also the addition of the PKS ausV diketide product to 1,2-dihydro-7-hydroxydehydroaustin, forming precalidodehydroaustin (PubMed:28233494). Finally, the iron/alpha-ketoglutarate-dependent dioxygenase converts precalidodehydroaustin into calidodehydroaustin (PubMed:28233494)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28233494"}],"value":"Secondary metabolite biosynthesis; terpenoid biosynthesis"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q70PR7"}],"value":"Monomer"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28233494"}],"value":"Leads to complete loss of production of austin"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"29076725"}],"value":"In A.calidoustus, the austinoid gene cluster lies on a contiguous DNA region, while clusters from E.nidulans and P.brasilianum are split in their respective genomes. Genetic rearrangements provoked variability among the clusters and E.nidulans produces the least number of austionoid derivatives with the end products austinol and dehydroaustinol, while P.brasilianum can produce until acetoxydehydroaustin, and A.calidoustus produces the highest number of identified derivatives"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the plant acyltransferase family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":480,"modifier":"EXACT"}},"description":"O-acyltransferase ausP","featureId":"PRO_0000453865"},{"type":"Active site","location":{"start":{"value":180,"modifier":"EXACT"},"end":{"value":180,"modifier":"EXACT"}},"description":"Proton acceptor","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q70PR7"}]},{"type":"Active site","location":{"start":{"value":412,"modifier":"EXACT"},"end":{"value":412,"modifier":"EXACT"}},"description":"Proton acceptor","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q70PR7"}]}],"keywords":[{"id":"KW-0012","category":"Molecular function","name":"Acyltransferase"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0808","category":"Molecular function","name":"Transferase"}],"references":[{"referenceNumber":1,"citation":{"id":"26966204","citationType":"journal article","authors":["Horn F.","Linde J.","Mattern D.J.","Walther G.","Guthke R.","Scherlach K.","Martin K.","Brakhage A.A.","Petzke L.","Valiante V."],"citationCrossReferences":[{"database":"PubMed","id":"26966204"},{"database":"DOI","id":"10.1128/genomea.00102-16"}],"title":"Draft genome sequences of fungus Aspergillus calidoustus.","publicationDate":"2016","journal":"Genome Announc.","firstPage":"0","lastPage":"0","volume":"4"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"SF006504","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"28233494","citationType":"journal article","authors":["Valiante V.","Mattern D.J.","Schueffler A.","Horn F.","Walther G.","Scherlach K.","Petzke L.","Dickhaut J.","Guthke R.","Hertweck C.","Nett M.","Thines E.","Brakhage A.A."],"citationCrossReferences":[{"database":"PubMed","id":"28233494"},{"database":"DOI","id":"10.1021/acschembio.7b00003"}],"title":"Discovery of an Extended Austinoid Biosynthetic Pathway in Aspergillus calidoustus.","publicationDate":"2017","journal":"ACS Chem. 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The first step of the pathway is the synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase ausA (PubMed:28233494). 3,5-dimethylorsellinic acid is then prenylated by the polyprenyl transferase ausN (PubMed:28233494). Further epoxidation by the FAD-dependent monooxygenase ausM and cyclization by the probable terpene cyclase ausL lead to the formation of protoaustinoid A (By similarity). Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by the combined action of the FAD-binding monooxygenases ausB and ausC, and the dioxygenase ausE (By similarity). Acid-catalyzed keto-rearrangement and ring contraction of the tetraketide portion of preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (By similarity). The aldo-keto reductase ausK, with the help of ausH, is involved in the next step by transforming preaustinoid A4 into isoaustinone which is in turn hydroxylated by the P450 monooxygenase ausI to form austinolide (By similarity). The cytochrome P450 monooxygenase ausG modifies austinolide to austinol (By similarity). Austinol is further acetylated to austin by the O-acetyltransferase ausP, which spontaneously changes to dehydroaustin (PubMed:28233494). The cytochrome P450 monooxygenase ausR then converts dehydroaustin is into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation catalyzed by ausR permits the O-acetyltransferase ausQ to add an additional acetyl group to the molecule, leading to the formation of acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase ausT catalyzes the reduction of the double bond present between carbon atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an acetylation reaction but also the addition of the PKS ausV diketide product to 1,2-dihydro-7-hydroxydehydroaustin, forming precalidodehydroaustin (PubMed:28233494). 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The pathway begins with the synthesis of the backbone drimenol by the terpene cyclase drtB using farnesyl pyrophosphate (FPP) as substrate (PubMed:34468074). The cytochrome P450 monooxygenase drtD is then responsible for the hydroxylations at C-6, C-9 and C-12, as well as the oxidation of hydroxyl groups at C-6 and C-11 to a ketone and an aldehyde, respectively (PubMed:34468074). Then, the biosynthesis can go in two directions, either the hydroxylated drimenol is further hydroxylated at C-2 and C-3 by an enzyme(s) not associated with the drt cluster, or the FAD-binding oxidoreductase drtC further oxidizes C-11 or C-12 to form the butyrolactone ring (PubMed:34468074). DrtB, drtD and drtC are solely responsible for the formation of the different drimane structures observed during drimane sesquiterpenes biosynthesis (PubMed:34468074). The polyketide synthase drtA synthesizes different lengths (C6 and C8) of PKS chains, which are then oxidized to varying degrees by the short-chain dehydrogenase drtF (PubMed:34468074). Finally, these PKS chains are transferred onto drimane sesquiterpenes by the acyltransferase drtE, forming the sesquiterpene esters (PubMed:34468074). In addition to the different fatty acyl-CoA chains produced by drtA, drtE is also able to use cinnamoyl-CoA as a substrate (PubMed:34468074)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}],"value":"Secondary metabolite biosynthesis; terpenoid biosynthesis"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}],"value":"Abolishes the production of asperiene C, asperiene A, calidoustene A, (6-Strobilactone-B) ester of (E,E)-6-carbonyl-7-hydroxy-2,4-octadienoic acid, ustusolate C, ustusolide E and calidoustene B (PubMed:34468074). Still produces ustusoic acid A, ustusolate A, (2'E,4'E)-6-(1'-carboxyhexa-2',4',-diene)-9-hydroxy-drim-7-ene-11,12-olide, calidoustene C and RES-1149-2, all compounds with fully unsaturated acyl chains (PubMed:34468074)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}],"value":"The various drimane-type sesquiterpene esters produced by the A.calidoustus drt cluster include asperiene C, asperiene A, (6-Strobilactone-B) ester of (E,E)-6-carbonyl-7-hydroxy-2,4-octadienoic acid, ustusolate A, ustusolate C, ustusolide E, ustusoic acid A, (2'E,4'E)-6-(1'-carboxyhexa-2',4',-diene)-9-hydroxy-drim-7-ene-11,12-olide, RES-1149-2, as well as the 3 newly identified compounds calidoustene A, calidoustene B and calidoustene C"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the short-chain dehydrogenases/reductases (SDR) family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":314,"modifier":"EXACT"}},"description":"Short-chain dehydrogenase/reductase drtF","featureId":"PRO_0000454535"},{"type":"Active site","location":{"start":{"value":185,"modifier":"EXACT"},"end":{"value":185,"modifier":"EXACT"}},"description":"Proton acceptor","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU10001"}]},{"type":"Active site","location":{"start":{"value":189,"modifier":"EXACT"},"end":{"value":189,"modifier":"EXACT"}},"description":"Lowers pKa of active site Tyr","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"O93868"}]},{"type":"Binding site","location":{"start":{"value":26,"modifier":"EXACT"},"end":{"value":26,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:58349"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"L0E2Z4"}],"ligand":{"name":"NADP(+)","id":"ChEBI:CHEBI:58349"}},{"type":"Binding site","location":{"start":{"value":50,"modifier":"EXACT"},"end":{"value":50,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:58349"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"L0E2Z4"}],"ligand":{"name":"NADP(+)","id":"ChEBI:CHEBI:58349"}},{"type":"Binding site","location":{"start":{"value":73,"modifier":"EXACT"},"end":{"value":73,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:58349"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"L0E2Z4"}],"ligand":{"name":"NADP(+)","id":"ChEBI:CHEBI:58349"}},{"type":"Binding site","location":{"start":{"value":100,"modifier":"EXACT"},"end":{"value":100,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:58349"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"O93868"}],"ligand":{"name":"NADP(+)","id":"ChEBI:CHEBI:58349"}},{"type":"Binding site","location":{"start":{"value":185,"modifier":"EXACT"},"end":{"value":185,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:58349"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"O93868"}],"ligand":{"name":"NADP(+)","id":"ChEBI:CHEBI:58349"}},{"type":"Binding site","location":{"start":{"value":189,"modifier":"EXACT"},"end":{"value":189,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:58349"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"O93868"}],"ligand":{"name":"NADP(+)","id":"ChEBI:CHEBI:58349"}}],"keywords":[{"id":"KW-0521","category":"Ligand","name":"NADP"},{"id":"KW-0560","category":"Molecular function","name":"Oxidoreductase"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"}],"references":[{"referenceNumber":1,"citation":{"id":"26966204","citationType":"journal article","authors":["Horn F.","Linde J.","Mattern D.J.","Walther G.","Guthke R.","Scherlach K.","Martin K.","Brakhage A.A.","Petzke L.","Valiante V."],"citationCrossReferences":[{"database":"PubMed","id":"26966204"},{"database":"DOI","id":"10.1128/genomea.00102-16"}],"title":"Draft genome sequences of fungus Aspergillus calidoustus.","publicationDate":"2016","journal":"Genome Announc.","firstPage":"0","lastPage":"0","volume":"4"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"SF006504","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"34468074","citationType":"journal article","authors":["Huang Y.","Hoefgen S.","Valiante V."],"citationCrossReferences":[{"database":"PubMed","id":"34468074"},{"database":"DOI","id":"10.1002/anie.202108970"}],"title":"Biosynthesis of fungal drimane-type sesquiterpene esters.","publicationDate":"2021","journal":"Angew. 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The first step of the pathway is the synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase ausA (PubMed:28233494). 3,5-dimethylorsellinic acid is then prenylated by the polyprenyl transferase ausN (PubMed:28233494). Further epoxidation by the FAD-dependent monooxygenase ausM and cyclization by the probable terpene cyclase ausL lead to the formation of protoaustinoid A (By similarity). Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by the combined action of the FAD-binding monooxygenases ausB and ausC, and the dioxygenase ausE (By similarity). Acid-catalyzed keto-rearrangement and ring contraction of the tetraketide portion of preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (By similarity). The aldo-keto reductase ausK, with the help of ausH, is involved in the next step by transforming preaustinoid A4 into isoaustinone which is in turn hydroxylated by the P450 monooxygenase ausI to form austinolide (By similarity). The cytochrome P450 monooxygenase ausG modifies austinolide to austinol (By similarity). Austinol is further acetylated to austin by the O-acetyltransferase ausP, which spontaneously changes to dehydroaustin (PubMed:28233494). The cytochrome P450 monooxygenase ausR then converts dehydroaustin is into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation catalyzed by ausR permits the O-acetyltransferase ausQ to add an additional acetyl group to the molecule, leading to the formation of acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase ausT catalyzes the reduction of the double bond present between carbon atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an acetylation reaction but also the addition of the PKS ausV diketide product to 1,2-dihydro-7-hydroxydehydroaustin, forming precalidodehydroaustin (PubMed:28233494). Finally, the iron/alpha-ketoglutarate-dependent dioxygenase converts precalidodehydroaustin into calidodehydroaustin (PubMed:28233494)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"28233494"}],"value":"Secondary metabolite biosynthesis; terpenoid biosynthesis"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"29076725"}],"value":"In A.calidoustus, the austinoid gene cluster lies on a contiguous DNA region, while clusters from E.nidulans and P.brasilianum are split in their respective genomes. 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The cytochrome P450 monooxygenase ausG modifies austinolide to austinol (By similarity). Austinol is further acetylated to austin by the O-acetyltransferase ausP, which spontaneously changes to dehydroaustin (PubMed:28233494). The cytochrome P450 monooxygenase ausR then converts dehydroaustin is into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation catalyzed by ausR permits the O-acetyltransferase ausQ to add an additional acetyl group to the molecule, leading to the formation of acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase ausT catalyzes the reduction of the double bond present between carbon atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an acetylation reaction but also the addition of the PKS ausV diketide product to 1,2-dihydro-7-hydroxydehydroaustin, forming precalidodehydroaustin (PubMed:28233494). Finally, the iron/alpha-ketoglutarate-dependent dioxygenase converts precalidodehydroaustin into calidodehydroaustin (PubMed:28233494)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"3,5-dimethylorsellinate + (2E,6E)-farnesyl diphosphate = (3R)-3-farnesyl-6-hydroxy-2,3,5-trimethyl-4-oxocyclohexa-1,5-diene-1-carboxylate + diphosphate + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:49632"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:33019"},{"database":"ChEBI","id":"CHEBI:131856"},{"database":"ChEBI","id":"CHEBI:131857"},{"database":"ChEBI","id":"CHEBI:175763"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q5AR21"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:49633"},"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q5AR21"}]}]},{"commentType":"COFACTOR","cofactors":[{"name":"Mg(2+)","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P32378"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:18420"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28233494"}],"value":"Secondary metabolite biosynthesis; terpenoid 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:0000269","source":"PubMed","id":"28233494"}],"value":"Impairs the biosynthesis of calidodehydroaustin and accumulates the intermediate compound 3,5-dimethylorsellinic acid"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"29076725"}],"value":"In A.calidoustus, the austinoid gene cluster lies on a contiguous DNA region, while clusters from E.nidulans and P.brasilianum are split in their respective genomes. Genetic rearrangements provoked variability among the clusters and E.nidulans produces the least number of austionoid derivatives with the end products austinol and dehydroaustinol, while P.brasilianum can produce until acetoxydehydroaustin, and A.calidoustus produces the highest number of identified derivatives"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the UbiA prenyltransferase family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":366,"modifier":"EXACT"}},"description":"Polyprenyl transferase ausN","featureId":"PRO_0000453860"},{"type":"Transmembrane","location":{"start":{"value":97,"modifier":"EXACT"},"end":{"value":117,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":121,"modifier":"EXACT"},"end":{"value":141,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":164,"modifier":"EXACT"},"end":{"value":184,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":215,"modifier":"EXACT"},"end":{"value":235,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":239,"modifier":"EXACT"},"end":{"value":259,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":287,"modifier":"EXACT"},"end":{"value":307,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":308,"modifier":"EXACT"},"end":{"value":328,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":346,"modifier":"EXACT"},"end":{"value":366,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]}],"keywords":[{"id":"KW-0460","category":"Ligand","name":"Magnesium"},{"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0808","category":"Molecular function","name":"Transferase"},{"id":"KW-0812","category":"Domain","name":"Transmembrane"},{"id":"KW-1133","category":"Domain","name":"Transmembrane helix"}],"references":[{"referenceNumber":1,"citation":{"id":"26966204","citationType":"journal article","authors":["Horn F.","Linde J.","Mattern D.J.","Walther G.","Guthke R.","Scherlach K.","Martin K.","Brakhage A.A.","Petzke L.","Valiante V."],"citationCrossReferences":[{"database":"PubMed","id":"26966204"},{"database":"DOI","id":"10.1128/genomea.00102-16"}],"title":"Draft genome sequences of fungus Aspergillus calidoustus.","publicationDate":"2016","journal":"Genome Announc.","firstPage":"0","lastPage":"0","volume":"4"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"SF006504","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"28233494","citationType":"journal article","authors":["Valiante V.","Mattern D.J.","Schueffler A.","Horn F.","Walther G.","Scherlach K.","Petzke L.","Dickhaut J.","Guthke R.","Hertweck C.","Nett M.","Thines E.","Brakhage A.A."],"citationCrossReferences":[{"database":"PubMed","id":"28233494"},{"database":"DOI","id":"10.1021/acschembio.7b00003"}],"title":"Discovery of an Extended Austinoid Biosynthetic Pathway in Aspergillus calidoustus.","publicationDate":"2017","journal":"ACS Chem. 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The pathway begins with the synthesis of the backbone drimenol by the terpene cyclase drtB using farnesyl pyrophosphate (FPP) as substrate (PubMed:34468074). The cytochrome P450 monooxygenase drtD is then responsible for the hydroxylations at C-6, C-9 and C-12, as well as the oxidation of hydroxyl groups at C-6 and C-11 to a ketone and an aldehyde, respectively (PubMed:34468074). Then, the biosynthesis can go in two directions, either the hydroxylated drimenol is further hydroxylated at C-2 and C-3 by an enzyme(s) not associated with the drt cluster, or the FAD-binding oxidoreductase drtC further oxidizes C-11 or C-12 to form the butyrolactone ring (PubMed:34468074). DrtB, drtD and drtC are solely responsible for the formation of the different drimane structures observed during drimane sesquiterpenes biosynthesis (PubMed:34468074). The polyketide synthase drtA synthesizes different lengths (C6 and C8) of PKS chains, which are then oxidized to varying degrees by the short-chain dehydrogenase drtF (PubMed:34468074). Finally, these PKS chains are transferred onto drimane sesquiterpenes by the acyltransferase drtE, forming the sesquiterpene esters (PubMed:34468074). In addition to the different fatty acyl-CoA chains produced by drtA, drtE is also able to use cinnamoyl-CoA as a substrate (PubMed:34468074)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"(2E,6E)-farnesyl diphosphate + H2O = (5S,9S,10S)-drim-7-en-11-ol + diphosphate","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:28290"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:33019"},{"database":"ChEBI","id":"CHEBI:61148"},{"database":"ChEBI","id":"CHEBI:175763"}],"ecNumber":"4.2.3.194","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:28291"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}]}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}],"value":"Secondary metabolite biosynthesis; terpenoid biosynthesis"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}],"value":"Abolished the drimane sesquiterpenes biosynthesis"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}],"value":"The various drimane-type sesquiterpene esters produced by the A.calidoustus drt cluster include asperiene C, asperiene A, (6-Strobilactone-B) ester of (E,E)-6-carbonyl-7-hydroxy-2,4-octadienoic acid, ustusolate A, ustusolate C, ustusolide E, ustusoic acid A, (2'E,4'E)-6-(1'-carboxyhexa-2',4',-diene)-9-hydroxy-drim-7-ene-11,12-olide, RES-1149-2, as well as the 3 newly identified compounds calidoustene A, calidoustene B and calidoustene C"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the HAD-like hydrolase superfamily"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":528,"modifier":"EXACT"}},"description":"Drimenol cyclase drtB","featureId":"PRO_0000454532"}],"keywords":[{"id":"KW-0456","category":"Molecular function","name":"Lyase"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"}],"references":[{"referenceNumber":1,"citation":{"id":"26966204","citationType":"journal article","authors":["Horn F.","Linde J.","Mattern D.J.","Walther G.","Guthke R.","Scherlach K.","Martin K.","Brakhage A.A.","Petzke L.","Valiante V."],"citationCrossReferences":[{"database":"PubMed","id":"26966204"},{"database":"DOI","id":"10.1128/genomea.00102-16"}],"title":"Draft genome sequences of fungus Aspergillus calidoustus.","publicationDate":"2016","journal":"Genome Announc.","firstPage":"0","lastPage":"0","volume":"4"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"SF006504","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"34468074","citationType":"journal article","authors":["Huang Y.","Hoefgen S.","Valiante V."],"citationCrossReferences":[{"database":"PubMed","id":"34468074"},{"database":"DOI","id":"10.1002/anie.202108970"}],"title":"Biosynthesis of fungal drimane-type sesquiterpene esters.","publicationDate":"2021","journal":"Angew. 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The pathway begins with the synthesis of the backbone drimenol by the terpene cyclase drtB using farnesyl pyrophosphate (FPP) as substrate (PubMed:34468074). The cytochrome P450 monooxygenase drtD is then responsible for the hydroxylations at C-6, C-9 and C-12, as well as the oxidation of hydroxyl groups at C-6 and C-11 to a ketone and an aldehyde, respectively (PubMed:34468074). Then, the biosynthesis can go in two directions, either the hydroxylated drimenol is further hydroxylated at C-2 and C-3 by an enzyme(s) not associated with the drt cluster, or the FAD-binding oxidoreductase drtC further oxidizes C-11 or C-12 to form the butyrolactone ring (PubMed:34468074). DrtB, drtD and drtC are solely responsible for the formation of the different drimane structures observed during drimane sesquiterpenes biosynthesis (PubMed:34468074). The polyketide synthase drtA synthesizes different lengths (C6 and C8) of PKS chains, which are then oxidized to varying degrees by the short-chain dehydrogenase drtF (PubMed:34468074). Finally, these PKS chains are transferred onto drimane sesquiterpenes by the acyltransferase drtE, forming the sesquiterpene esters (PubMed:34468074). In addition to the different fatty acyl-CoA chains produced by drtA, drtE is also able to use cinnamoyl-CoA as a substrate (PubMed:34468074)"}],"commentType":"FUNCTION"},{"commentType":"COFACTOR","cofactors":[{"name":"FAD","evidences":[{"evidenceCode":"ECO:0000305"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:57692"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}],"value":"Secondary metabolite biosynthesis; terpenoid biosynthesis"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}],"value":"Leads to disappearance of all compounds harboring a gamma-butyrolactone ring or containing a carboxylic acid at C-11, but accumulates ustusolate A"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34468074"}],"value":"The various drimane-type sesquiterpene esters produced by the A.calidoustus drt cluster include asperiene C, asperiene A, (6-Strobilactone-B) ester of (E,E)-6-carbonyl-7-hydroxy-2,4-octadienoic acid, ustusolate A, ustusolate C, ustusolide E, ustusoic acid A, (2'E,4'E)-6-(1'-carboxyhexa-2',4',-diene)-9-hydroxy-drim-7-ene-11,12-olide, RES-1149-2, as well as the 3 newly identified compounds calidoustene A, calidoustene B and calidoustene C"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the oxygen-dependent FAD-linked oxidoreductase family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":523,"modifier":"EXACT"}},"description":"FAD-dependent monooxygenase drtC","featureId":"PRO_5006858084"},{"type":"Domain","location":{"start":{"value":77,"modifier":"EXACT"},"end":{"value":252,"modifier":"EXACT"}},"description":"FAD-binding PCMH-type","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00718"}]}],"keywords":[{"id":"KW-0274","category":"Ligand","name":"FAD"},{"id":"KW-0285","category":"Ligand","name":"Flavoprotein"},{"id":"KW-0560","category":"Molecular function","name":"Oxidoreductase"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"}],"references":[{"referenceNumber":1,"citation":{"id":"26966204","citationType":"journal article","authors":["Horn F.","Linde J.","Mattern D.J.","Walther G.","Guthke R.","Scherlach K.","Martin K.","Brakhage A.A.","Petzke L.","Valiante V."],"citationCrossReferences":[{"database":"PubMed","id":"26966204"},{"database":"DOI","id":"10.1128/genomea.00102-16"}],"title":"Draft genome sequences of fungus Aspergillus calidoustus.","publicationDate":"2016","journal":"Genome Announc.","firstPage":"0","lastPage":"0","volume":"4"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"SF006504","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"34468074","citationType":"journal article","authors":["Huang Y.","Hoefgen S.","Valiante V."],"citationCrossReferences":[{"database":"PubMed","id":"34468074"},{"database":"DOI","id":"10.1002/anie.202108970"}],"title":"Biosynthesis of fungal drimane-type sesquiterpene esters.","publicationDate":"2021","journal":"Angew. 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The first step of the pathway is the synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase ausA (PubMed:28233494). 3,5-dimethylorsellinic acid is then prenylated by the polyprenyl transferase ausN (PubMed:28233494). Further epoxidation by the FAD-dependent monooxygenase ausM and cyclization by the probable terpene cyclase ausL lead to the formation of protoaustinoid A (By similarity). Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by the combined action of the FAD-binding monooxygenases ausB and ausC, and the dioxygenase ausE (By similarity). Acid-catalyzed keto-rearrangement and ring contraction of the tetraketide portion of preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (By similarity). The aldo-keto reductase ausK, with the help of ausH, is involved in the next step by transforming preaustinoid A4 into isoaustinone which is in turn hydroxylated by the P450 monooxygenase ausI to form austinolide (By similarity). The cytochrome P450 monooxygenase ausG modifies austinolide to austinol (By similarity). Austinol is further acetylated to austin by the O-acetyltransferase ausP, which spontaneously changes to dehydroaustin (PubMed:28233494). The cytochrome P450 monooxygenase ausR then converts dehydroaustin is into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation catalyzed by ausR permits the O-acetyltransferase ausQ to add an additional acetyl group to the molecule, leading to the formation of acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase ausT catalyzes the reduction of the double bond present between carbon atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an acetylation reaction but also the addition of the PKS ausV diketide product to 1,2-dihydro-7-hydroxydehydroaustin, forming precalidodehydroaustin (PubMed:28233494). Finally, the iron/alpha-ketoglutarate-dependent dioxygenase converts precalidodehydroaustin into calidodehydroaustin (PubMed:28233494)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"protoaustinoid A + AH2 + O2 = berkeleyone A + A + H2O","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:65140"},{"database":"ChEBI","id":"CHEBI:13193"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15379"},{"database":"ChEBI","id":"CHEBI:17499"},{"database":"ChEBI","id":"CHEBI:69024"},{"database":"ChEBI","id":"CHEBI:156350"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q5ATK1"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:65141"},"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q5ATK1"}]}]},{"commentType":"COFACTOR","cofactors":[{"name":"FAD","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"H3JQW0"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:57692"}}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"H3JQW0"}],"value":"Binds 1 FAD per subunit."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"28233494"}],"value":"Secondary metabolite biosynthesis; terpenoid biosynthesis"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"29076725"}],"value":"In A.calidoustus, the austinoid gene cluster lies on a contiguous DNA region, while clusters from E.nidulans and P.brasilianum are split in their respective genomes. Genetic rearrangements provoked variability among the clusters and E.nidulans produces the least number of austionoid derivatives with the end products austinol and dehydroaustinol, while P.brasilianum can produce until acetoxydehydroaustin, and A.calidoustus produces the highest number of identified derivatives"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the FAD-binding monooxygenase family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":632,"modifier":"EXACT"}},"description":"FAD-binding monooxygenase ausB","featureId":"PRO_0000453846"},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":50,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional 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