DRTC_ASPCI
ID DRTC_ASPCI Reviewed; 523 AA.
AC A0A0U5GQ05;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 16-MAR-2016, sequence version 1.
DT 03-AUG-2022, entry version 17.
DE RecName: Full=FAD-dependent monooxygenase drtC {ECO:0000303|PubMed:34468074};
DE EC=1.-.-.- {ECO:0000269|PubMed:34468074};
DE AltName: Full=Drimane-type sesquiterpene ester biosynthesis cluster protein C {ECO:0000303|PubMed:34468074};
GN Name=drtC {ECO:0000303|PubMed:34468074}; ORFNames=ASPCAL02979;
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: FAD-dependent 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=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:34468074}.
CC -!- DISRUPTION PHENOTYPE: Leads to disappearance of all compounds harboring
CC a gamma-butyrolactone ring or containing a carboxylic acid at C-11, but
CC accumulates ustusolate A. {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 oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; CDMC01000002; CEN60543.1; -; Genomic_DNA.
DR EnsemblFungi; CEN60543; CEN60543; ASPCAL02979.
DR OrthoDB; 733611at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000054771; Unassembled WGS sequence.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Oxidoreductase; Reference proteome.
FT CHAIN 1..523
FT /note="FAD-dependent monooxygenase drtC"
FT /id="PRO_5006858084"
FT DOMAIN 77..252
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
SQ SEQUENCE 523 AA; 57042 MW; 0CD92BE891D914E9 CRC64;
MLFAKAFQSA TVAGAVILAA LVDVAHSTPL DDPGQCGLEA VAQCCTSLRE SAVGDKVFAY
GDIEYFRAKR SYYSVTTSLN SACIVLPESA EDVSTVLTTL TQPDLAETCP FAIRSGGHSM
VVGFSDIAAG VTLDLSKLNH TIYHPETETV SLGPGGRWVN VYEELRPDNV MVSGGRFSSV
GVGGFLTGGG ITIYSAQRGL ACDDVVSFDV VLANGTLIQA TNATNPDLFH TLKGGSGNLG
VVTNFEVRAF PQTQIWGGYT SYNVSKTPEL ARTLQNFTSN IEQDPKALLV TFWTYDTLTD
VNRAANAMYY TDPVEYPEAF NDYYAIENIS STVHTRSIES LVTELEDTTN WFRVLFVTLA
FKNDARVIEH GANLYQEYID TIKANVSGGD WLVIAGFQPM PTLFGTSGQE NGGNIIGLEN
NGDKIVLLFE AFWERTQDDE LFEPLADELI HNLEEYARSL EQDSDFLYLN YADGWQDPIS
GYGGDNIEQL RAAAEKYDPN GVFQTQVPGG FKISKVPVAE QKK
