PENG_PENCR
ID PENG_PENCR Reviewed; 341 AA.
AC A0A0E3D8P4;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 24-JUN-2015, sequence version 1.
DT 03-AUG-2022, entry version 16.
DE RecName: Full=Geranylgeranyl pyrophosphate synthase penG {ECO:0000303|PubMed:26213965};
DE Short=GGPP synthase {ECO:0000305};
DE Short=GGPPSase {ECO:0000305};
DE EC=2.5.1.- {ECO:0000305};
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 protein G {ECO:0000303|PubMed:26213965};
GN Name=penG {ECO:0000303|PubMed:26213965};
OS Penicillium crustosum (Blue mold fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=36656;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, FUNCTION, AND PATHWAY.
RC STRAIN=PN2402;
RX PubMed=26213965; DOI=10.3390/toxins7082701;
RA Nicholson M.J., Eaton C.J., Starkel C., Tapper B.A., Cox M.P., Scott B.;
RT "Molecular cloning and functional analysis of gene clusters for the
RT biosynthesis of indole-diterpenes in Penicillium crustosum and P.
RT janthinellum.";
RL Toxins 7:2701-2722(2015).
CC -!- FUNCTION: Geranylgeranyl pyrophosphate synthase; part of the gene
CC cluster that mediates the biosynthesis of the indole diterpenes
CC penitrems (PubMed:26213965). The geranylgeranyl diphosphate (GGPP)
CC synthase penG catalyzes the first step in penitrem biosynthesis via
CC conversion of farnesyl pyrophosphate and isopentyl pyrophosphate into
CC geranylgeranyl pyrophosphate (GGPP) (Probable). Condensation of indole-
CC 3-glycerol phosphate with GGPP by the prenyl transferase penC then
CC forms 3-geranylgeranylindole (3-GGI) (Probable). Epoxidation by the
CC FAD-dependent monooxygenase penM leads to a epoxidized-GGI that is
CC substrate of the terpene cyclase penB for cyclization to yield
CC paspaline (Probable). Paspaline is subsequently converted to 13-
CC desoxypaxilline by the cytochrome P450 monooxygenase penP, the latter
CC being then converted to paxilline by the cytochrome P450 monooxygenase
CC penQ (PubMed:26213965). Paxilline is converted to beta-paxitriol via C-
CC 10 ketoreduction by the short-chain dehydrogenase PC-15 which can be
CC monoprenylated at the C-20 by the indole diterpene prenyltransferase
CC penD (Probable). A two-step elimination (acetylation and elimination)
CC process performed by the O-acetyltransferase PC-16 and the
CC P.simplicissimum ptmI-ortholog not yet identified in P.crustosum, leads
CC to the production of the prenylated form of penijanthine (Probable).
CC The FAD-linked oxidoreductase ptmO then converts the prenylated form of
CC penijanthine into PC-M5 which is in turn transformed into PC-M4 by the
CC aromatic dimethylallyltransferase PC-22 (Probable). A series of
CC oxidation steps involving 4 cytochrome P450 monooxygenases (PC-21, PC-
CC 05, PC-23, PC-20) and a FAD-dependent monooxygenase (PC-14) are
CC required for the transformation of PC-M4 to penitrems A and E.
CC Synthesis of these final products is proposed to proceed via penitrems
CC D and C (PC-21, PC-05, PC-14) and penitrems B and F (PC-21, PC-05, PC-
CC 14, PC-23) (Probable). {ECO:0000269|PubMed:26213965,
CC ECO:0000305|PubMed:26213965}.
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:0000305|PubMed:26213965}.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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DR EMBL; KC963408; AGZ20182.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A0E3D8P4; -.
DR SMR; A0A0E3D8P4; -.
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:UniProtKB-KW.
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 Isoprene biosynthesis; Magnesium; Metal-binding; Transferase.
FT CHAIN 1..341
FT /note="Geranylgeranyl pyrophosphate synthase penG"
FT /id="PRO_0000446552"
FT BINDING 68
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 71
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 100
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 107
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 107
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 111
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 111
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 116
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 117
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 194
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 195
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 228
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 231
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 235
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 245
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 255
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT SITE 139
FT /note="Important for determining product chain length"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
SQ SEQUENCE 341 AA; 38580 MW; FADAA1CD96772393 CRC64;
MLFLAPGYIF PNVATPVTVA IDFAQAVKQG AYNVLDLKAS PIPNPELFQP PSRIIRGPLN
YLLSLPGKDI RGKLIDALNE WFRVPEDKLN IIKEIVVILH TASLLIDDIQ DSSELRRGNP
VAHRIFGVAQ TINSANYAYF LAQAKLADLN DSRAFDIFTK GLLKLHRGQG MELYWRDNLI
CPTEEEYVEM VSCKTGGLFY LAVQLMQLNS EVTVNFSNFI NLLGIIFQIR DDYMNLQSGT
MTKTKGFSED LTEGKFGYPI IHSIHAAPND SQLIQILKLK TKDEVIKQYA VRYIESTGSF
VYCREKLDMY LEEANETFRG LEMLLGPSKG IRAILDFLRT R
