PTMG_PENSI
ID PTMG_PENSI Reviewed; 356 AA.
AC A0A140JWS2;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 11-MAY-2016, sequence version 1.
DT 03-AUG-2022, entry version 14.
DE RecName: Full=Geranylgeranyl pyrophosphate synthase penG {ECO:0000303|PubMed:25831977};
DE Short=GGPP synthase {ECO:0000305};
DE Short=GGPPSase {ECO:0000305};
DE EC=2.5.1.- {ECO:0000269|PubMed:25831977};
DE AltName: Full=(2E,6E)-farnesyl diphosphate synthase {ECO:0000250|UniProtKB:Q12051};
DE AltName: Full=Dimethylallyltranstransferase {ECO:0000250|UniProtKB:Q12051};
DE EC=2.5.1.1 {ECO:0000250|UniProtKB:Q12051};
DE AltName: Full=Farnesyl diphosphate synthase {ECO:0000250|UniProtKB:Q12051};
DE AltName: Full=Farnesyltranstransferase {ECO:0000250|UniProtKB:Q12051};
DE EC=2.5.1.29 {ECO:0000250|UniProtKB:Q12051};
DE AltName: Full=Geranylgeranyl diphosphate synthase {ECO:0000250|UniProtKB:Q12051};
DE AltName: Full=Geranyltranstransferase {ECO:0000250|UniProtKB:Q12051};
DE EC=2.5.1.10 {ECO:0000250|UniProtKB:Q12051};
DE AltName: Full=Penitrem biosynthesis cluster 1 protein G {ECO:0000303|PubMed:25831977};
GN Name=ptmG {ECO:0000303|PubMed:25831977};
OS Penicillium simplicissimum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=69488;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, FUNCTION, AND PATHWAY.
RC STRAIN=AK-40;
RX PubMed=25831977; DOI=10.1002/anie.201501072;
RA Liu C., Tagami K., Minami A., Matsumoto T., Frisvad J.C., Suzuki H.,
RA Ishikawa J., Gomi K., Oikawa H.;
RT "Reconstitution of biosynthetic machinery for the synthesis of the highly
RT elaborated indole diterpene penitrem.";
RL Angew. Chem. Int. Ed. 54:5748-5752(2015).
CC -!- FUNCTION: Geranylgeranyl pyrophosphate synthase; part of the gene
CC cluster that mediates the biosynthesis of the indole diterpenes
CC penitrems (PubMed:25831977). The geranylgeranyl diphosphate (GGPP)
CC synthase ptmG catalyzes the first step in penitrem biosynthesis via
CC conversion of farnesyl pyrophosphate and isopentyl pyrophosphate into
CC geranylgeranyl pyrophosphate (GGPP) (PubMed:25831977). Condensation of
CC indole-3-glycerol phosphate with GGPP by the prenyl transferase ptmC
CC then forms 3-geranylgeranylindole (3-GGI) (PubMed:25831977).
CC Epoxidation by the FAD-dependent monooxygenase ptmM leads to a
CC epoxidized-GGI that is substrate of the terpene cyclase ptmB for
CC cyclization to yield paspaline (PubMed:25831977). Paspaline is
CC subsequently converted to 13-desoxypaxilline by the cytochrome P450
CC monooxygenase ptmP, the latter being then converted to paxilline by the
CC cytochrome P450 monooxygenase ptmQ (PubMed:25831977). Paxilline is
CC converted to beta-paxitriol via C-10 ketoreduction by the short-chain
CC dehydrogenase ptmH which can be monoprenylated at the C-20 by the
CC indole diterpene prenyltransferase ptmD (PubMed:25831977). A two-step
CC elimination (acetylation and elimination) process performed by the O-
CC acetyltransferase ptmV and ptmI leads to the production of the
CC prenylated form of penijanthine (PubMed:25831977). The FAD-linked
CC oxidoreductase ptmO then converts the prenylated form of penijanthine
CC into PC-M5 which is in turn transformed into PC-M4 by the aromatic
CC dimethylallyltransferase ptmE (PubMed:25831977). Five sequential
CC oxidative transformations performed by the cytochrome P450
CC monooxygenases ptmK, ptmU, ptmL, ptmN and ptmJ yield the various
CC penitrem compounds. PtmK, ptmU and ptmM are involved in the formation
CC of the key bicyclic ring of penitrem C via the formation of the
CC intermediates secopenitrem D and penitrem D. PtmL catalyzes the
CC epoxidation of penitrem D and C to yield penitrem B and F,
CC respectively. PtmJ catalyzes the last benzylic hydroxylation to convert
CC penitrem B to prenitrem E and penitrem F to penitrem A
CC (PubMed:25831977). {ECO:0000269|PubMed:25831977}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dimethylallyl diphosphate + isopentenyl diphosphate = (2E)-
CC geranyl diphosphate + diphosphate; Xref=Rhea:RHEA:22408,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57623, ChEBI:CHEBI:58057,
CC ChEBI:CHEBI:128769; EC=2.5.1.1;
CC Evidence={ECO:0000250|UniProtKB:Q12051};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-geranyl diphosphate + isopentenyl diphosphate = (2E,6E)-
CC farnesyl diphosphate + diphosphate; Xref=Rhea:RHEA:19361,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:58057, ChEBI:CHEBI:128769,
CC ChEBI:CHEBI:175763; EC=2.5.1.10;
CC Evidence={ECO:0000250|UniProtKB:Q12051};
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:0000250|UniProtKB:Q12051};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q12051};
CC Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q12051};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:25831977}.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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DR EMBL; LC027936; BAU61549.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A140JWS2; -.
DR SMR; A0A140JWS2; -.
DR GO; GO:0004161; F:dimethylallyltranstransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0004311; F:farnesyltranstransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0004337; F:geranyltranstransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:InterPro.
DR CDD; cd00685; Trans_IPPS_HT; 1.
DR Gene3D; 1.10.600.10; -; 1.
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; 1.
DR PROSITE; PS00723; POLYPRENYL_SYNTHASE_1; 1.
DR PROSITE; PS00444; POLYPRENYL_SYNTHASE_2; 1.
PE 3: Inferred from homology;
KW Magnesium; Metal-binding; Transferase.
FT CHAIN 1..356
FT /note="Geranylgeranyl pyrophosphate synthase penG"
FT /id="PRO_0000446553"
FT BINDING 83
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 86
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 115
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 122
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 122
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 126
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 126
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 131
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 132
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 209
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 210
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 243
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 246
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 250
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 260
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 270
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT SITE 154
FT /note="Important for determining product chain length"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
SQ SEQUENCE 356 AA; 40178 MW; EE95A86FC0CCF51B CRC64;
MLFLAPGYIF PHVATPVTVA IDFAQAVKEG AYSFLDLKAS PVPNPELFQP PSRVSIGMTG
GREERNEEII RGPLNYLLSL PGKDIRGKLI DALNEWFRVP EDKLSTIKEI IVILHTASLL
IDDIQDSSQL RRGNPVAHRI FGVAQTINSA NYAYFLAQAK LADLNDSRAF DIFTKGLLKL
HRGQGMELYW RDNLICPTEE EYVEMVSCKT GGLFYLAVQL MQLNSEVTVN FSSFINLLGI
IFQIRDDYMN LQSGTMTKTK GFSEDLTEGK FGYPIIHSIH AAPNDQQLIQ ILKLKTNDEV
IKQYAVRYIE STGSFIYCRE KLDLYLQEAN ETFQGLELLL GPSKGIRAIL NFLRTR
