TPCA_COCH5
ID TPCA_COCH5 Reviewed; 704 AA.
AC M2U578;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 1.
DT 03-AUG-2022, entry version 36.
DE RecName: Full=Preterpestacin I synthase tpcA {ECO:0000303|PubMed:29185768};
DE AltName: Full=Aspergilol biosynthesis cluster protein tpcA {ECO:0000303|PubMed:29185768};
DE AltName: Full=Bifunctional terpene synthase tpcA {ECO:0000303|PubMed:29185768};
DE Short=BFTS tpcA {ECO:0000303|PubMed:29185768};
DE Short=TS tpcA {ECO:0000303|PubMed:29185768};
DE Includes:
DE RecName: Full=Terpene cyclase {ECO:0000303|PubMed:29185768};
DE EC=4.2.3.- {ECO:0000269|PubMed:29185768};
DE Includes:
DE RecName: Full=Geranylgeranyl diphosphate synthase {ECO:0000303|PubMed:29185768};
DE Short=GGDP synthase {ECO:0000303|PubMed:29185768};
DE Short=GGS {ECO:0000303|PubMed:29185768};
DE EC=2.5.1.29 {ECO:0000269|PubMed:29185768};
DE Includes:
DE RecName: Full=Geranylfarnesyl diphosphate synthase {ECO:0000303|PubMed:29185768};
DE Short=GFDP synthase {ECO:0000303|PubMed:29185768};
DE EC=2.5.1.81 {ECO:0000269|PubMed:29185768};
GN Name=tpcA {ECO:0000303|PubMed:29417814};
GN Synonyms=BmTS3 {ECO:0000303|PubMed:29185768}; ORFNames=COCHEDRAFT_1171743;
OS Cochliobolus heterostrophus (strain C5 / ATCC 48332 / race O) (Southern
OS corn leaf blight fungus) (Bipolaris maydis).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Pleosporomycetidae; Pleosporales; Pleosporineae; Pleosporaceae; Bipolaris.
OX NCBI_TaxID=701091;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C5 / ATCC 48332 / race O;
RX PubMed=23236275; DOI=10.1371/journal.ppat.1003037;
RA Ohm R.A., Feau N., Henrissat B., Schoch C.L., Horwitz B.A., Barry K.W.,
RA Condon B.J., Copeland A.C., Dhillon B., Glaser F., Hesse C.N., Kosti I.,
RA LaButti K., Lindquist E.A., Lucas S., Salamov A.A., Bradshaw R.E.,
RA Ciuffetti L., Hamelin R.C., Kema G.H.J., Lawrence C., Scott J.A.,
RA Spatafora J.W., Turgeon B.G., de Wit P.J.G.M., Zhong S., Goodwin S.B.,
RA Grigoriev I.V.;
RT "Diverse lifestyles and strategies of plant pathogenesis encoded in the
RT genomes of eighteen Dothideomycetes fungi.";
RL PLoS Pathog. 8:E1003037-E1003037(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C5 / ATCC 48332 / race O;
RX PubMed=23357949; DOI=10.1371/journal.pgen.1003233;
RA Condon B.J., Leng Y., Wu D., Bushley K.E., Ohm R.A., Otillar R., Martin J.,
RA Schackwitz W., Grimwood J., MohdZainudin N., Xue C., Wang R., Manning V.A.,
RA Dhillon B., Tu Z.J., Steffenson B.J., Salamov A., Sun H., Lowry S.,
RA LaButti K., Han J., Copeland A., Lindquist E., Barry K., Schmutz J.,
RA Baker S.E., Ciuffetti L.M., Grigoriev I.V., Zhong S., Turgeon B.G.;
RT "Comparative genome structure, secondary metabolite, and effector coding
RT capacity across Cochliobolus pathogens.";
RL PLoS Genet. 9:E1003233-E1003233(2013).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=29185768; DOI=10.1021/acs.orglett.7b03418;
RA Narita K., Sato H., Minami A., Kudo K., Gao L., Liu C., Ozaki T.,
RA Kodama M., Lei X., Taniguchi T., Monde K., Yamazaki M., Uchiyama M.,
RA Oikawa H.;
RT "Focused genome mining of structurally related sesterterpenes: enzymatic
RT formation of enantiomeric and diastereomeric products.";
RL Org. Lett. 19:6696-6699(2017).
RN [4]
RP FUNCTION, AND PATHWAY.
RX PubMed=29417814; DOI=10.1021/acs.joc.7b03220;
RA Narita K., Minami A., Ozaki T., Liu C., Kodama M., Oikawa H.;
RT "Total biosynthesis of antiangiogenic agent (-)-terpestacin by artificial
RT reconstitution of the biosynthetic machinery in Aspergillus oryzae.";
RL J. Org. Chem. 83:7042-7048(2018).
CC -!- FUNCTION: Bifunctional terpene synthase; part of the gene cluster that
CC mediates the biosynthesis of terpestacin (PubMed:29185768). The
CC bifunctional terpene synthase tpcA converts isopentenyl diphosphate
CC (IPP) and dimethylallyl diphosphate (DMAPP) into the sesterterpene
CC preterpestacin I (PubMed:29185768). The C-terminal prenyltransferase
CC (PT) domain of tpcA catalyzes formation of GFPP, whereas the N-terminal
CC terpene cyclase (TC) domain catalyzes the cyclization of GFPP into
CC preterpestacin I (PubMed:29185768). The cytochrome P450 monooxygenase
CC tpcB then hydroxylates preterpestacin I to yield 24-
CC hydroxypreterpstacin I (renamed as preterpestacin II) whereas the
CC cytochrome P450 monooxygenase tpcC further hydroxylates preterpestacin
CC II to yield 16,17-dihydroxypreterpestacin II (renamed as preterpestacin
CC III) (PubMed:29417814). Finally, the FAD-dependent monooxygenase tpcD
CC converts preterpestacin III into terpestacin (PubMed:29417814).
CC {ECO:0000269|PubMed:29185768, ECO:0000269|PubMed:29417814}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate =
CC (2E,6E,10E)-geranylgeranyl diphosphate + diphosphate;
CC Xref=Rhea:RHEA:17653, ChEBI:CHEBI:33019, ChEBI:CHEBI:58756,
CC ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.29;
CC Evidence={ECO:0000269|PubMed:29185768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17654;
CC Evidence={ECO:0000269|PubMed:29185768};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E,10E)-geranylgeranyl diphosphate + isopentenyl
CC diphosphate = (2E,6E,10E,14E)-geranylfarnesyl diphosphate +
CC diphosphate; Xref=Rhea:RHEA:25694, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57907, ChEBI:CHEBI:58756, ChEBI:CHEBI:128769;
CC EC=2.5.1.81; Evidence={ECO:0000269|PubMed:29185768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25695;
CC Evidence={ECO:0000269|PubMed:29185768};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P9WEV7};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:29185768}.
CC -!- SUBUNIT: Hexamer. {ECO:0000250|UniProtKB:A2PZA5}.
CC -!- DOMAIN: The conserved DDXXD motifs as well as the NSE/DTE motif are
CC important for the catalytic activity, presumably through binding to
CC Mg(2+). {ECO:0000250|UniProtKB:P9WEP0}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the terpene synthase
CC family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the FPP/GGPP synthase
CC family. {ECO:0000305}.
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DR EMBL; KB445573; EMD93704.1; -; Genomic_DNA.
DR SMR; M2U578; -.
DR STRING; 701091.M2U578; -.
DR EnsemblFungi; EMD93704; EMD93704; COCHEDRAFT_1171743.
DR eggNOG; KOG0777; Eukaryota.
DR HOGENOM; CLU_014015_10_0_1; -.
DR OMA; FSWEREY; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000016936; Unassembled WGS sequence.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.600.10; -; 2.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR000092; Polyprenyl_synt.
DR InterPro; IPR033749; Polyprenyl_synt_CS.
DR Pfam; PF00348; polyprenyl_synt; 1.
DR SUPFAM; SSF48576; SSF48576; 2.
DR PROSITE; PS00723; POLYPRENYL_SYNTHASE_1; 1.
DR PROSITE; PS00444; POLYPRENYL_SYNTHASE_2; 1.
PE 1: Evidence at protein level;
KW Isoprene biosynthesis; Lyase; Magnesium; Metal-binding;
KW Multifunctional enzyme; Reference proteome; Repeat; Transferase.
FT CHAIN 1..704
FT /note="Preterpestacin I synthase tpcA"
FT /id="PRO_0000453706"
FT REGION 1..329
FT /note="Terpene cyclase"
FT /evidence="ECO:0000250|UniProtKB:P9WEP0"
FT REGION 330..688
FT /note="Prenyltransferase"
FT /evidence="ECO:0000250|UniProtKB:P9WEP0"
FT REGION 361..380
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 96..100
FT /note="DDXXD 1"
FT /evidence="ECO:0000250|UniProtKB:P9WEP0"
FT MOTIF 231..239
FT /note="NSE/DTE"
FT /evidence="ECO:0000250|UniProtKB:P9WEP0"
FT MOTIF 445..449
FT /note="DDXXD 2"
FT /evidence="ECO:0000250|UniProtKB:P9WEP0"
FT BINDING 96
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 96
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 96
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 231
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 235..239
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 325..326
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 406
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 409
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 438
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 445
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 445
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 449
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 449
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 454
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 455
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 532
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 533
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 568
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 575
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 583
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 593
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
SQ SEQUENCE 704 AA; 79402 MW; 50E3A04C8F82452B CRC64;
MEQLSYQSKL ICSDESRHTG CFTTLPIRIH PRDDLADAAS RRFVQDWARE MRDGREQSTH
FSFSPVGNWS SLIYPEAIPE RLGVLAYLSD LGLIHDDGGE GLSIEDAQAE HGELCAALDP
SDISSAAPGS RAMKTKKLVS QCMLECISLD RELGLKMLAA FRDVWLAISE RNSDKEAQTM
EEYLKYRSDN GGMLVFWPML QFSLGMSISE AEEALVQPII DAATEGLLLA NDYFSWEREY
RELQSGQSKR IVSAVDLFIR TKGLSIDDAK EEVKRKIIAA ERDFCQRRDD LYTNHPNIPL
KLKRWIDCAG LAVSGNHYWC SACPRQNAWK DMSSQSLNGA KRKTSHGATI GMHEAPFKKR
KDSSFFGSQP SDDEPSLSEV SSYPFYKPSG LALEAPSKYV SDMPSKGVRS TLIEALNTWL
HVPSERLDSI MSVINTLHNA SLILDDLEDN SPLRRGYPAT HILFGHSQSI NTANFMFVRA
VQEVAQNLSP NALVALLEEL KGLYLGQSWD LYWKHNLACP SEAEYVNMID HKTGGMFRML
LRIMQAESDV TPQPDFHRLT LLFGRFFQIR DDYMNFQDYT AQKGLCEDLD EGKFSYPVVY
CLENHPEYRG YFLSMFRQRP TIATVNACPL SGESKQYLTA CLKKSGAFNK TIACLTDMER
DLEFEINRLE QQTGETNPML RLCLAKLSVK GIGRIGEVSP STSK
