SDNC_SORAA
ID SDNC_SORAA Reviewed; 533 AA.
AC A0A1B4XBK0;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2016, sequence version 1.
DT 03-AUG-2022, entry version 14.
DE RecName: Full=Geranylgeranyl diphosphate synthase sdnC {ECO:0000303|PubMed:27072286};
DE EC=2.5.1.- {ECO:0000305|PubMed:27072286};
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 pyrophosphate synthase {ECO:0000305};
DE Short=GGPP synthase {ECO:0000305};
DE Short=GGPPSase {ECO:0000305};
DE AltName: Full=Geranyltranstransferase {ECO:0000250|UniProtKB:Q12051};
DE EC=2.5.1.10 {ECO:0000250|UniProtKB:Q12051};
DE AltName: Full=Sordarin/hypoxysordarin biosynthesis cluster protein C {ECO:0000303|PubMed:27072286};
GN Name=sdnC {ECO:0000303|PubMed:27072286};
OS Sordaria araneosa (Pleurage araneosa).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Sordariaceae; Sordaria.
OX NCBI_TaxID=573841;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC STRAIN=ATCC 36386 / NRRL 3196;
RX PubMed=27072286; DOI=10.1038/ja.2016.40;
RA Kudo F., Matsuura Y., Hayashi T., Fukushima M., Eguchi T.;
RT "Genome mining of the sordarin biosynthetic gene cluster from Sordaria
RT araneosa Cain ATCC 36386: characterization of cycloaraneosene synthase and
RT GDP-6-deoxyaltrose transferase.";
RL J. Antibiot. 69:541-548(2016).
CC -!- FUNCTION: Geranylgeranyl diphosphate synthase; part of the gene cluster
CC that mediates the biosynthesis of sordarin and hypoxysordarin,
CC glycoside antibiotics with a unique tetracyclic diterpene aglycone
CC structure (PubMed:27072286). First, the geranylgeranyl diphosphate
CC synthase sdnC constructs GGDP from farnesyl diphosphate and isopentenyl
CC diphosphate (PubMed:27072286). The diterpene cyclase sdnA then
CC catalyzes the cyclization of GGDP to afford cycloaraneosene
CC (PubMed:27072286). Cycloaraneosene is then hydroxylated four times by
CC the putative cytochrome P450 monooxygenases sdnB, sdnE, sdnF and sdnH
CC to give a hydroxylated cycloaraneosene derivative such as
CC cycloaraneosene-8,9,13,19-tetraol (PubMed:27072286). Although the order
CC of the hydroxylations is unclear, at least C8, C9 and C13 of the
CC cycloaraneosene skeleton are hydroxylated before the sordaricin
CC formation (PubMed:27072286). Dehydration of the 13-hydroxy group of the
CC hydroxylated cycloaraneosene derivative might be catalyzed by an
CC unassigned hypothetical protein such as sdnG and sdnP to construct the
CC cyclopentadiene moiety (PubMed:27072286). The FAD-dependent
CC oxidoreductase sdnN is proposed to catalyze the oxidation at C9 of the
CC hydroxylated cycloaraneosene derivative and also catalyze the Baeyer-
CC Villiger oxidation to give the lactone intermediate (PubMed:27072286).
CC The presumed lactone intermediate would be hydrolyzed to give an
CC acrolein moiety and a carboxylate moiety (PubMed:27072286). Then,
CC [4+2]cycloaddition would occur between the acrolein moiety and the
CC cyclopentadiene moiety to give sordaricin (PubMed:27072286). SdnN might
CC also be involved in the [4+2]cycloaddition after the hypothesized
CC oxidation to accommodate the oxidized product and prompt the
CC [4+2]cycloaddition (PubMed:27072286). GDP-6-deoxy-D-altrose may be
CC biosynthesized from GDP-D-mannose by the putative GDP-mannose-4,6-
CC dehydratase sdnI and the short-chain dehydrogenase sdnK
CC (PubMed:27072286). The glycosyltransferase sdnJ catalyzes the
CC attachment of 6-deoxy-D-altrose onto the 19-hydroxy group of sordaricin
CC to give 4'-O-demethylsordarin (PubMed:27072286). The methyltransferase
CC sdnD would complete the biosynthesis of sordarin (PubMed:27072286).
CC Sordarin can be further modified into hypoxysordarin (PubMed:27072286).
CC The unique acyl chain at the 3'-hydroxy group of hypoxysordarin would
CC be constructed by an iterative type I PKS sdnO and the trans-acting
CC polyketide methyltransferase sdnL. SdnL would be responsible for the
CC introduction of an alpha-methyl group of the polyketide chain
CC (PubMed:27072286). Alternatively, the beta-lactamase-like protein sdnR
CC might be responsible for the cleavage and transfer of the polyketide
CC chain from the PKS sdnO to sordarin (PubMed:27072286). Two putative
CC cytochrome P450 monooxygenases, sdnQ and sdnT, might catalyze the
CC epoxidations of the polyketide chain to complete the biosynthesis of
CC hypoxysordarin (PubMed:27072286). Transcriptional regulators sdnM and
CC sdnS are presumably encoded for the transcriptional regulation of the
CC expression of the sdn gene cluster (PubMed:27072286).
CC {ECO:0000269|PubMed:27072286}.
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: Antibiotic biosynthesis. {ECO:0000305|PubMed:27072286}.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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DR EMBL; LC079035; BAV32147.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1B4XBK0; -.
DR SMR; A0A1B4XBK0; -.
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: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 Antibiotic biosynthesis; Isoprene biosynthesis; Magnesium; Metal-binding;
KW Transferase.
FT CHAIN 1..533
FT /note="Geranylgeranyl diphosphate synthase sdnC"
FT /id="PRO_0000441055"
FT REGION 98..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 187..206
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 98..137
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 238
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 241
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 270
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 277
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 277
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 281
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 281
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 286
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 287
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 364
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 365
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 412
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 415
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 419
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 429
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 439
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
SQ SEQUENCE 533 AA; 58261 MW; 73FF407C5599FC02 CRC64;
MSFDQFAPFM TLGRPDAVCD ECSRPVAPNS ISDDDAAVNT TETDTQHANI PEEQDVINIK
LDSTFNAESS AETIDLKVEG VKLAIVSQQP TYEAITAETT SSVATSEEAS SDTATSLTNL
TSREPSPSSS SASSVAEECP SEEPASDDTV PAASEKNHPD GTLNPNYHDA RADEVHPQHE
VVQVQAPHLP PPQGVQPAAT ENPDHDSLFS VFTQDHNPLL SGTIVGAPAD YVASTPGKKI
RDKAASALNI WLQVSPDDLN QIRTVIDMLH NASLILDDVE DGSVSRRGRP ATHMIFGMPQ
AINSAGYQIN RAMMEVLKLG SQDCLEIFIE ELDRLYIGQG YDLFWTFNIK RPSVEKYISM
VDYKTGSLFN MLVRFMAAKT GAKGGVETDN NKAPIAPPDL TRLVVLLGRY FQIRDDYMNL
TSDEYTLQKG FCDDLDEGKF SLTLVHALEN SPEAEKSILR HLLTQRLSSN GQGMSLAQKH
LVIDIVKGAG SLEYTVTALR KIGMEIVNEL DQIEGVTGIE NKELRRLVEV LRV
