PLE4_CLIPA
ID PLE4_CLIPA Reviewed; 350 AA.
AC A0A2L0VXR5;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 25-APR-2018, sequence version 1.
DT 03-AUG-2022, entry version 15.
DE RecName: Full=Geranylgeranyl pyrophosphate synthase {ECO:0000303|PubMed:27143514};
DE Short=GGPP synthase {ECO:0000250|UniProtKB:Q12051};
DE Short=GGPPSase {ECO:0000250|UniProtKB:Q12051};
DE Short=GGS {ECO:0000303|PubMed:27143514};
DE EC=2.5.1.- {ECO:0000250|UniProtKB:Q12051};
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=Pleuromutilin biosynthetic cluster protein synthesis protein G {ECO:0000303|PubMed:27143514};
GN Name=GGPS {ECO:0000303|PubMed:27143514};
GN Synonyms=ggs {ECO:0000303|PubMed:27143514};
OS Clitopilus passeckerianus (Pleurotus passeckerianus).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Entolomataceae; Clitopilus.
OX NCBI_TaxID=648682;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, FUNCTION, INDUCTION, AND
RP PATHWAY.
RX PubMed=27143514; DOI=10.1038/srep25202;
RA Bailey A.M., Alberti F., Kilaru S., Collins C.M., de Mattos-Shipley K.,
RA Hartley A.J., Hayes P., Griffin A., Lazarus C.M., Cox R.J., Willis C.L.,
RA O'Dwyer K., Spence D.W., Foster G.D.;
RT "Identification and manipulation of the pleuromutilin gene cluster from
RT Clitopilus passeckerianus for increased rapid antibiotic production.";
RL Sci. Rep. 6:25202-25202(2016).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND PATHWAY.
RX PubMed=29388775; DOI=10.1021/acs.orglett.8b00121;
RA Xu M., Jia M., Hong Y.J., Yin X., Tantillo D.J., Proteau P.J., Peters R.J.;
RT "Premutilin synthase: ring rearrangement by a class II diterpene cyclase.";
RL Org. Lett. 20:1200-1202(2018).
CC -!- FUNCTION: Geranylgeranyl pyrophosphate synthase; part of the gene
CC cluster that mediates the biosynthesis of pleuromutilin, a tricyclic
CC diterpene showing antibacterial properties (PubMed:27143514,
CC PubMed:29388775). The geranylgeranyl diphosphate (GGPP) synthase
CC catalyzes the first step in pleuromutilin biosynthesis
CC (PubMed:27143514, PubMed:29388775). GGPP is then substrate of the
CC premutilin synthase (PS) to yield premutilin (PubMed:29388775).
CC Premutilin synthase is a bifunctional enzyme composed of the fusion of
CC a class II diterpene cyclase (DTC) and a class I diterpene synthase
CC (DTS), with the corresponding domains and active sites containing
CC characteristic aspartate-rich motifs. GGPP is first converted to
CC mutildienyl-diphosphate (MPP) at the class II DTC site
CC (PubMed:29388775). MPP is subsequently further cyclized at the class I
CC DTS site, followed by a 1,5-hydride shift and addition of water prior
CC to terminating deprotonation, to yield premutilin (PubMed:29388775). In
CC addition to the aforementioned GGPP synthase and bifunctional diterpene
CC synthase, the cluster contains also three cytochrome P450
CC monooxygenases, a short-chain alcohol dehydrogenase, and an
CC acyltransferase, involved in the conversion of premutilin to
CC pleuromutilin (PubMed:27143514, PubMed:29388775). The cytochrome P450
CC monooxygenases P450-1 and P450-2 hydroxylate premutilin at C-11 and C-
CC 3, respectively, producing 11-hydroxypremutilin and 3-hydroxypremutilin
CC (By similarity). The combination of the actions of both ple5 and ple6
CC leads to the production of 3,11-dihydroxypremutilin (By similarity).
CC The short chain dehydrogenase SDR further converts 3,11-
CC dihydroxypremutilin into mutilin (By similarity). The acetyltransferase
CC ATF then acetylates mutilin to produce 14-O-acetylmutilin (By
CC similarity). Finally, the cytochrome P450 monooxygenase P450-3
CC catalyzes hydroxylation on the alpha position of the acetyl side chain
CC of 14-O-acetylmutilin to yield pleuromutilin (By similarity).
CC {ECO:0000250|UniProtKB:A0A6S6QJ62, ECO:0000269|PubMed:27143514,
CC ECO:0000269|PubMed:29388775}.
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 2 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q12051};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:27143514, ECO:0000269|PubMed:29388775}.
CC -!- INDUCTION: Expression is up-regulated during pleuromutilin production.
CC {ECO:0000269|PubMed:27143514}.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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DR EMBL; MG764076; AVA16671.1; -; mRNA.
DR AlphaFoldDB; A0A2L0VXR5; -.
DR SMR; A0A2L0VXR5; -.
DR UniPathway; UPA00213; -.
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:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
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 2: Evidence at transcript level;
KW Antibiotic biosynthesis; Isoprene biosynthesis; Magnesium; Metal-binding;
KW Transferase.
FT CHAIN 1..350
FT /note="Geranylgeranyl pyrophosphate synthase"
FT /id="PRO_0000445370"
FT BINDING 66
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 69
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 98
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 105
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 105
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 109
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 109
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 114
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
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 200
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 201
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 236
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 263
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT SITE 137
FT /note="Important for determining product chain length"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
SQ SEQUENCE 350 AA; 39229 MW; E42E4BF0B0FA2A2C CRC64;
MRIPNVFLSY LRQVAVDGTL SSCSGVKSRK PVIAYGFDDS QDSLVDENDE KILEPFGYYR
HLLKGKSART VLMHCFNAFL GLPEDWVIGV TKAIEDLHNA SLLIDDIEDE SALRRGSPAA
HMKYGIALTM NAGNLVYFTV LQDVYDLGMK TGGTQVANAM ARIYTEEMIE LHRGQGIEIW
WRDQRSPPSV DQYIHMLEQK TGGLLRLGVR LLQCHPGVNN RADLSDIALR IGVYYQLRDD
YINLMSTSYH DERGFAEDMT EGKYTFPMLH SLKRSPDSGL REILDLKPAD IALKKKAIAI
MQDTGSLVAT RNLLGAVKND LSGLVAEQRG DDYAMSAGLE RFLEKLYIAE
