DRTF_ASPCI
ID DRTF_ASPCI Reviewed; 314 AA.
AC A0A0U5CNP2;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 16-MAR-2016, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Short-chain dehydrogenase/reductase drtF {ECO:0000303|PubMed:34468074};
DE EC=1.1.1.- {ECO:0000269|PubMed:34468074};
DE AltName: Full=Drimane-type sesquiterpene ester biosynthesis cluster protein F {ECO:0000303|PubMed:34468074};
GN Name=drtF {ECO:0000303|PubMed:34468074}; ORFNames=ASPCAL02982;
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: Short-chain dehydrogenase/reductase; part of the gene cluster
CC that mediates the biosynthesis of various drimane-type sesquiterpene
CC esters, compounds that exhibit diverse biological activities and are
CC widely present in eukaryotes (PubMed:34468074). The pathway begins with
CC the synthesis of the backbone drimenol by the terpene cyclase drtB
CC using 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 -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:34468074}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of asperiene C,
CC asperiene A, calidoustene A, (6-Strobilactone-B) ester of (E,E)-6-
CC carbonyl-7-hydroxy-2,4-octadienoic acid, ustusolate C, ustusolide E and
CC calidoustene B (PubMed:34468074). Still produces ustusoic acid A,
CC ustusolate A, (2'E,4'E)-6-(1'-carboxyhexa-2',4',-diene)-9-hydroxy-drim-
CC 7-ene-11,12-olide, calidoustene C and RES-1149-2, all compounds with
CC fully unsaturated acyl chains (PubMed:34468074).
CC {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 short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; CDMC01000002; CEN60546.1; -; Genomic_DNA.
DR STRING; 454130.A0A0U5CNP2; -.
DR EnsemblFungi; CEN60546; CEN60546; ASPCAL02982.
DR OrthoDB; 921996at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000054771; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW NAD; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..314
FT /note="Short-chain dehydrogenase/reductase drtF"
FT /id="PRO_0000454535"
FT ACT_SITE 185
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 18..26
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 45..46
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 76..78
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 185..189
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 225..227
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
SQ SEQUENCE 314 AA; 34079 MW; 4EC3A2E09B70F0C1 CRC64;
MAPALPFALP SLAGKVYLVT GGNTGVGFHT VDELAKHGAR VYMGARSPGK AEAAIKTIRA
ETPTADVHFL QMDLMDLHSV VAAAKSFKEK ETKLHGLVNN AGIMATPYAL SGDGFEAQWQ
TNYLSHWVLT WHLLDVLVRT LQAEGGAAGS VRVVDVTSDG HNFAPKVGID FKDINLEKAG
VFARYGQSKV GNILHAKQLN KLYGPSGSET AKKGIWTAAV HPGHLDTNLN KQTAFPKFVN
TLLRAVGAYS PPRDGAFNSV FAVASPEFKV ADSGEYFVPG QKKKQPSKVA RDMELAGRLW
KWTEEELRKR ELLD
