ID   DRTD_ASPCI              Reviewed;         524 AA.
AC   A0A0U5GRB4;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   16-MAR-2016, sequence version 1.
DT   03-AUG-2022, entry version 16.
DE   RecName: Full=Cytochrome P450 monooxygenase drtD {ECO:0000303|PubMed:34468074};
DE            EC=1.-.-.- {ECO:0000269|PubMed:34468074};
DE   AltName: Full=Drimane-type sesquiterpene ester biosynthesis cluster protein D {ECO:0000303|PubMed:34468074};
GN   Name=drtD {ECO:0000303|PubMed:34468074}; ORFNames=ASPCAL02980;
OS   Aspergillus calidoustus.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Nidulantes.
OX   NCBI_TaxID=454130;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=SF006504;
RX   PubMed=26966204; DOI=10.1128/genomea.00102-16;
RA   Horn F., Linde J., Mattern D.J., Walther G., Guthke R., Scherlach K.,
RA   Martin K., Brakhage A.A., Petzke L., Valiante V.;
RT   "Draft genome sequences of fungus Aspergillus calidoustus.";
RL   Genome Announc. 4:0-0(2016).
RN   [2]
RP   FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=34468074; DOI=10.1002/anie.202108970;
RA   Huang Y., Hoefgen S., Valiante V.;
RT   "Biosynthesis of fungal drimane-type sesquiterpene esters.";
RL   Angew. Chem. Int. Ed. 60:23763-23770(2021).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of various drimane-type sesquiterpene esters,
CC       compounds that exhibit diverse biological activities and are widely
CC       present in eukaryotes (PubMed:34468074). The pathway begins with the
CC       synthesis of the backbone drimenol by the terpene cyclase drtB using
CC       farnesyl pyrophosphate (FPP) as substrate (PubMed:34468074). The
CC       cytochrome P450 monooxygenase drtD is then responsible for the
CC       hydroxylations at C-6, C-9 and C-12, as well as the oxidation of
CC       hydroxyl groups at C-6 and C-11 to a ketone and an aldehyde,
CC       respectively (PubMed:34468074). Then, the biosynthesis can go in two
CC       directions, either the hydroxylated drimenol is further hydroxylated at
CC       C-2 and C-3 by an enzyme(s) not associated with the drt cluster, or the
CC       FAD-binding oxidoreductase drtC further oxidizes C-11 or C-12 to form
CC       the butyrolactone ring (PubMed:34468074). DrtB, drtD and drtC are
CC       solely responsible for the formation of the different drimane
CC       structures observed during drimane sesquiterpenes biosynthesis
CC       (PubMed:34468074). The polyketide synthase drtA synthesizes different
CC       lengths (C6 and C8) of PKS chains, which are then oxidized to varying
CC       degrees by the short-chain dehydrogenase drtF (PubMed:34468074).
CC       Finally, these PKS chains are transferred onto drimane sesquiterpenes
CC       by the acyltransferase drtE, forming the sesquiterpene esters
CC       (PubMed:34468074). In addition to the different fatty acyl-CoA chains
CC       produced by drtA, drtE is also able to use cinnamoyl-CoA as a substrate
CC       (PubMed:34468074). {ECO:0000269|PubMed:34468074}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:34468074}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of all the drimane
CC       sesquiterpene. {ECO:0000269|PubMed:34468074}.
CC   -!- MISCELLANEOUS: The various drimane-type sesquiterpene esters produced
CC       by the A.calidoustus drt cluster include asperiene C, asperiene A, (6-
CC       Strobilactone-B) ester of (E,E)-6-carbonyl-7-hydroxy-2,4-octadienoic
CC       acid, ustusolate A, ustusolate C, ustusolide E, ustusoic acid A,
CC       (2'E,4'E)-6-(1'-carboxyhexa-2',4',-diene)-9-hydroxy-drim-7-ene-11,12-
CC       olide, RES-1149-2, as well as the 3 newly identified compounds
CC       calidoustene A, calidoustene B and calidoustene C.
CC       {ECO:0000269|PubMed:34468074}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; CDMC01000002; CEN60544.1; -; Genomic_DNA.
DR   EnsemblFungi; CEN60544; CEN60544; ASPCAL02980.
DR   OrthoDB; 702827at2759; -.
DR   UniPathway; UPA00213; -.
DR   Proteomes; UP000054771; Unassembled WGS sequence.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR   GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002401; Cyt_P450_E_grp-I.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; SSF48264; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   1: Evidence at protein level;
KW   Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..524
FT                   /note="Cytochrome P450 monooxygenase drtD"
FT                   /id="PRO_0000454533"
FT   TRANSMEM        2..22
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         418
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:P04798"
SQ   SEQUENCE   524 AA;  59303 MW;  F7C7AFC2A8D7D5BA CRC64;
     MSDTYLVAAS GLAVCFFVLY LLRPKTALPP GPPKLPLIGN LHQLGKKPMY ERCQEWHRQF
     GKLISLKLGF DNVVVIGSSQ IARDLLDKKG AMYSSRPKFV MAHENVTKGF HTATLPYGPR
     WRLHNRMQLS VLNKRIVTRC RQVQEFESLQ LIHELLFTND FHPRFQRWAN SLQTGLGYGQ
     RLAKGDECNI HEMEHISRVF REIFATGTWL VDLFPALNHL PPLLAPWKGV AEQHYNRTIE
     LFQLNTAAAL SKTSWNWTKK IRSLTESQGL PPDEVNFLVG VMAEAGGDTT GVVLDMFTLA
     AALHPEKMAI AQKEIDTVVG TDRLPNFGDV DKLPYLAALI KECLRWHPAA PFGLPHSVMQ
     DDTYDGYHIP AGTTIIASQW SINFDPETFP NPYEFRPERY LENPDLPISS FGFGRRACPG
     RYFAMDSLFI SISRVLWTFN IRPIKQGKDD PPMPAWEFVM DGALLRPAPF KALFSARDIH
     RQRFVIKEWA AAEKSVDVEA LYDAIEPAGG DFSAQEKEEP VLVA