DRTA_ASPCI
ID DRTA_ASPCI Reviewed; 2359 AA.
AC A0A0U4ZX08;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 16-MAR-2016, sequence version 1.
DT 03-AUG-2022, entry version 30.
DE RecName: Full=Low-reducing polyketide synthase drtA {ECO:0000303|PubMed:34468074};
DE EC=2.3.1.- {ECO:0000269|PubMed:34468074};
DE AltName: Full=Drimane-type sesquiterpene ester biosynthesis cluster protein A {ECO:0000303|PubMed:34468074};
GN Name=drtA {ECO:0000303|PubMed:34468074}; ORFNames=ASPCAL02977;
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, DOMAIN, 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: Low-reducing polyketide synthase; 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 -!- DOMAIN: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; an enoylreductase (ER)
CC domain that reduces enoyl groups to alkyl group; a ketoreductase (KR)
CC domain that catalyzes beta-ketoreduction steps; and an acyl-carrier
CC protein (ACP) that serves as the tether of the growing and completed
CC polyketide via its phosphopantetheinyl arm.
CC {ECO:0000305|PubMed:34468074}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of all the sesquiterpene
CC ester compounds. {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}.
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DR EMBL; CDMC01000002; CEN60541.1; -; Genomic_DNA.
DR EnsemblFungi; CEN60541; CEN60541; ASPCAL02977.
DR OrthoDB; 19161at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000054771; Unassembled WGS sequence.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR013154; ADH_N.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 3.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Multifunctional enzyme; NADP; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..2359
FT /note="Low-reducing polyketide synthase drtA"
FT /id="PRO_0000454531"
FT DOMAIN 2280..2356
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:34468074"
FT REGION 20..447
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:34468074"
FT REGION 556..868
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:34468074"
FT REGION 940..1245
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:34468074"
FT REGION 1659..1970
FT /note="Enoyl reductase (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:34468074"
FT REGION 1995..2172
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:34468074"
FT ACT_SITE 190
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 190
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 648
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 972
FT /note="For beta-hydroxyacyl dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2316
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2359 AA; 254219 MW; B2691DB3EBD8FF7A CRC64;
MDNTPDTLSI SEEAAGLPPI AVVSFACRLP GQNSDPEALW RFLERGQTAS NEVPESRFSA
QAHYDGTRRP RTMKGRGGMF LHDVDPARFD APFFNISAVE ARSMDPQQRQ LLEVVYEALE
NGGLTLDGIS GEQIGCFVSS FTTDFLALQN RDPDDRPINL TTGTKRSIMS NRISHYFNIK
GPSMTVDTAC SGGLTSVDLA CRYLAANDIS AAVVAASHLF LNPDELLEEG QVGSVYSRTG
LCQVFDAKAD GYVKAEAVNA VILKRLDQAV ADGDPIRAVI RASASNSNGA TVGISTPSAE
QQAACIRAAY KRAGISDFNA TAYVECHGTG TQAGDPIEVN GLSAVFGGTR DPQAPLILGS
VKGNLGHSEP AAGISGLIKA VLSIEKGKIP GQSTLKELNP KIDLLGGALQ IPTKTISWPA
VPLRRVSVNS FGFGGANAHV IVEEPKGSLG EEWSKPHASS RSSQALASRQ STSKKLYTMV
FSAASEESLK RYYTDIKRHL ADLNVKVKPS DLAYTLGQRR THHAYRGYVV TSAANLNRAK
VEFGEKGMEP PKVAFVFTGQ GSQWPQMGAG LIKNFPCAAK RLRYLDTVLQ STSTPPSWSL
VDELSEPRQA DYYQKPELSQ PLITALQLAI LSILEEWGVL PRAVVGHSSG EIAAAYAAGY
LSQEQAILAA FYRGQAAAVL GPTIVEPLGM CAVGAGTEQL KQLLPDMPRE VQVACVNSPN
SVTLSGPKSH LVGVQAQLEA QGTFARLLRV DLAYHSSYVA DIAALYKKQL EAEWAKYPAP
ARASDAAQMF SSVTGHLLDQ PCDSEYWRVN MASPVLFSDA AAELVKDSSA TLLLEIGPSG
ALAGPVRQIL EGISVKGVQY LAALDRGKDG GEAMHELAGK LYVADYPLSL GAVNFPSADE
PTSRPSVLVD LPNYSWDHSA VYWHESDASK DWRFGQFPYH ELLGRKILGT PWSAPSWKSI
IRLDDMPWLK DHRMAGDPVF PAAGYLAMAI EAVYQARQSV NPIPDVAGVT DLQFVLRDVN
FRRALALDSG KDTTVVLAFT EVSDDYTSWT GFRVLSIQEG TSVTHCDGRI SVRQVAARAA
DKETLAPLAY SESAEHWYRA LDHRGCTYGP DFQRLLEIEC RAGQQETRST LSRNPPSTGF
PQHPYAMHPS TLDICFQSVF PALYSGLRSE IKSLLLPSHL EELTVGPSGG LPAEGETAVS
VARAGHSGAG AKEKRRNHYT DASVWSTSTG QLLLEFKGLR FSELNMGDGV DADPALLVPA
WLPDFEFLSQ DQILTVLRPE SAVADVINLV ASKKPTLRVG EINLTSDSVS TAWFEGASEG
LRGASEHYTY ADPDSARLST VRSSVGDRPN AEFKLLGKDA NAIFADPGVD LVIVQYQDLV
ATAQTSVLER IKPSEAKGDV VYLFVQRSAT TPSGEDADEA LLQDAGFNTL FKIPIDGSSF
AYLSRSIELA TPPSEQEEPQ VISIISADPQ SGLLNTFTES LTEAGYAVQL QTTFGAPTND
VKAVVVLDDF SSPVLGDVTD EQWTSIRDLV LKAPSTIWVT QGAQHKVTNP NNALIHGLSR
SIRSENPAVR LVTLDVESKS PRDNSVTILK LLDSIASREG GSGEDSEFVE RDGILHVSRT
LRKADAEELN VNDAPATAPN AQSLLDNAKH VKLGITNLGS FDSLELYEAT GEEPPLAADQ
VEIEVYATGL NYKDVQISTG AIPGDDQALG FDGAGSVTKV GQNVHTFRVG DKVAFTDSGA
FANRVRTTYK RVHHVPDGMA LEVAAALPLS FMTAIYALVN IAGLRKGQSV LIHSGAGGVG
IAAIQLAQYL QAEIYVTVGS DEKRSFLQEH LNIPASRIFS SRTTEFADAI IASTKGRGVD
VILNSLTGEL LDETWRICAD GGILVDIGRG LRGRRLAPGP FERNCLVKAF DLTSKQVSDD
IVRSLLTQAF GLFEKQHLQL IHPVRAFSYA EIRQAFEHLS TGRHVGKVVV SHGSDNGAVP
IRPAPSLSVI RKDRSYLITG GLHGIGGTLA EYLALRGAKC IVVLSRSGSS TPRAAWIVET
CRRLGCEIQV VKGDVTSYES IKGALQQAKL PVCGIVHGAM VLLDKPYELM DADSYRRCIA
PKVRGAWNLH QAAEELGLEL DFFTLLSSIS GVIGQSGQAN YAAANSFLDS FAAYRRGLGL
PALSLDIGAV QDTGVAMENP GLLHYFTDPQ WLNIEQGELF YLMDASIKEQ QNARNAPSSQ
LIMALSFPLP ATSDLLNDIR FRTLSRAGTS NQPAQNSANQ ESQAVTDFLC MQSSGADSTA
LTEAAIELFQ SQLLRMLRLD EPIKANKPLS AYGMDSLSAV KLRNWVEKSF SVTFAVFEIL
GANGLQALCS KLITRLQTV
