VRTD_PENAE
ID VRTD_PENAE Reviewed; 349 AA.
AC D7PHZ5;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 1.
DT 03-AUG-2022, entry version 35.
DE RecName: Full=Farnesyl pyrophosphate synthase vrtD {ECO:0000250|UniProtKB:P08524};
DE Short=FPP synthase {ECO:0000250|UniProtKB:P08524};
DE Short=FPS {ECO:0000250|UniProtKB:P08524};
DE EC=2.5.1.10 {ECO:0000250|UniProtKB:P08524, ECO:0000305};
DE AltName: Full=(2E,6E)-farnesyl diphosphate synthase {ECO:0000250|UniProtKB:P08524, ECO:0000305};
DE AltName: Full=Dimethylallyltranstransferase {ECO:0000250|UniProtKB:P08524};
DE EC=2.5.1.1 {ECO:0000250|UniProtKB:P08524};
DE AltName: Full=Farnesyl diphosphate synthase {ECO:0000250|UniProtKB:P08524, ECO:0000305};
DE AltName: Full=Viridicatumtoxin synthesis protein D {ECO:0000303|PubMed:20534346};
GN Name=vrtD {ECO:0000303|PubMed:20534346};
OS Penicillium aethiopicum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=36650;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=IBT 5753;
RX PubMed=20534346; DOI=10.1016/j.chembiol.2010.03.015;
RA Chooi Y.H., Cacho R., Tang Y.;
RT "Identification of the viridicatumtoxin and griseofulvin gene clusters from
RT Penicillium aethiopicum.";
RL Chem. Biol. 17:483-494(2010).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=19168978; DOI=10.1038/ja.2008.84;
RA Zheng C.J., Yu H.E., Kim E.H., Kim W.G.;
RT "Viridicatumtoxin B, a new anti-MRSA agent from Penicillium sp. FR11.";
RL J. Antibiot. 61:633-637(2008).
RN [3]
RP FUNCTION.
RX PubMed=24161266; DOI=10.1021/ja408966t;
RA Chooi Y.H., Hong Y.J., Cacho R.A., Tantillo D.J., Tang Y.;
RT "A cytochrome P450 serves as an unexpected terpene cyclase during fungal
RT meroterpenoid biosynthesis.";
RL J. Am. Chem. Soc. 135:16805-16808(2013).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=27049441; DOI=10.1038/ja.2016.35;
RA Inokoshi J., Nakamura Y., Komada S., Komatsu K., Umeyama H., Tomoda H.;
RT "Inhibition of bacterial undecaprenyl pyrophosphate synthase by small
RT fungal molecules.";
RL J. Antibiot. 69:798-805(2016).
CC -!- FUNCTION: Farnesyl pyrophosphate synthase; part of the gene cluster
CC that mediates the biosynthesis of viridicatumtoxin, a tetracycline-like
CC fungal meroterpenoid with a unique, fused spirobicyclic ring system
CC (PubMed:20534346). The first step of the pathway is the production of
CC the malonamoyl-CoA starter unit for the polyketide synthase vrtA
CC (PubMed:20534346). The aldolase vrtJ may be involved in the synthesis
CC of the malonamate substrate for malonamoyl-CoA synthetase vrtB
CC (PubMed:20534346). The polyketide synthase vrtA then may utilize the
CC malonamoyl-CoA starter unit, followed by sequential condensation of
CC eight malonyl-CoA units to form the polyketide backbone
CC (PubMed:20534346). The cyclization of the last ring could be mediated
CC by the lactamase-like protein vrtG (PubMed:20534346). The proposed
CC post-PKS tailoring steps are an hydroxylation at C5 catalyzed the
CC cytochrome P450 monooxygenase vrtE, a hydroxylation at C12a catalyzed
CC by VrtH and/or VrtI, and an O-methylation by the O-methyltransferase
CC vrtF (PubMed:20534346, PubMed:24161266). VrtC is then proposed to
CC catalyze the transfer of a geranyl group synthesized by vrtD to the
CC aromatic C ring of the tetracyclic polyketide intermediate of
CC viridicatumtoxin to yield previridicatumtoxin (PubMed:20534346).
CC Finally, the cytochrome P450 monooxygenase vrtK catalyzes the
CC spirocyclization of the geranyl moiety of previridicatumtoxin to afford
CC viridicatumtoxin (PubMed:24161266). {ECO:0000269|PubMed:20534346,
CC ECO:0000269|PubMed:24161266}.
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:P14324};
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:P14324};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P14324};
CC Note=Binds 2 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:P14324};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:20534346}.
CC -!- BIOTECHNOLOGY: Viridicatumtoxin and its derivative, viridicatumtoxin B,
CC exhibit anti-methicillin-resistant Staphylococcus aureus (anti-MRSA)
CC activity (PubMed:19168978). Moreover, viridicatumtoxin and a C2 acetyl
CC analog, spirohexaline, have been demonstrated to inhibit bacterial
CC undecaprenyl diphosphate synthase, a potential new target for
CC antibiotic development (PubMed:27049441). {ECO:0000269|PubMed:19168978,
CC ECO:0000269|PubMed:27049441}.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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DR EMBL; GU574477; ADI24929.1; -; Genomic_DNA.
DR AlphaFoldDB; D7PHZ5; -.
DR SMR; D7PHZ5; -.
DR BioCyc; MetaCyc:MON-19278; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0004161; F:dimethylallyltranstransferase 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:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00685; Trans_IPPS_HT; 1.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR039702; FPS1-like.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR000092; Polyprenyl_synt.
DR InterPro; IPR033749; Polyprenyl_synt_CS.
DR PANTHER; PTHR11525; PTHR11525; 1.
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 1: Evidence at protein level;
KW Magnesium; Metal-binding; Transferase.
FT CHAIN 1..349
FT /note="Farnesyl pyrophosphate synthase vrtD"
FT /id="PRO_0000436827"
FT BINDING 53
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 56
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 92
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 99
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 99
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 103
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 103
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 108
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 109
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 196
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 197
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 236
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 253
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 262
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:P14324"
SQ SEQUENCE 349 AA; 38652 MW; 3CB4C1E0F98E1BF7 CRC64;
MATSTTTSLK EFLSVFPQLV ADLRALCLEE YQLPACVWDR FESTLNHNTL GGKCNRGLSV
IDSVRLLRDG LELSPAEYFD AAVLGWLVEL LQATMLVLDD IMDGSPTRRG KPSWYRVPGV
GMAAVNDATM LESAIYMLLK KYFAGRAIYL PVVDLFHETA LQIELGQAFD MLIANEGTPD
LTTFVPATYS QIVTYKTAFY SFYLPVALAL HAVDAATPTN LAAARAILVP MGEYFQVQDD
YLDCFADPTV LGKVGTDIIE GKCSWLVVQA LQRASTDQAQ LLAENYGSAS GESSVKALYS
ELDLESVYRT FEEQRVAELR TLITGLDESQ GLRKSVFEEL LGKIYQRRK
