SDNI_SORAA
ID SDNI_SORAA Reviewed; 544 AA.
AC A0A1B4XBH2;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2016, sequence version 1.
DT 03-AUG-2022, entry version 15.
DE RecName: Full=GDP-mannose 4,6-dehydratase sdnI {ECO:0000303|PubMed:27072286};
DE EC=4.2.1.47 {ECO:0000250|UniProtKB:P93031};
DE AltName: Full=Sordarin/hypoxysordarin biosynthesis cluster protein I {ECO:0000303|PubMed:27072286};
GN Name=sdnI {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: GDP-mannose 4,6-dehydratase; part of the gene cluster that
CC mediates the biosynthesis of sordarin and hypoxysordarin, glycoside
CC antibiotics with a unique tetracyclic diterpene aglycone structure
CC (PubMed:27072286). First, the geranylgeranyl diphosphate synthase sdnC
CC constructs GGDP from farnesyl diphosphate and isopentenyl diphosphate
CC (PubMed:27072286). The diterpene cyclase sdnA then catalyzes the
CC cyclization of GGDP to afford cycloaraneosene (PubMed:27072286).
CC Cycloaraneosene is then hydroxylated four times by the putative
CC cytochrome P450 monooxygenases sdnB, sdnE, sdnF and sdnH to give a
CC hydroxylated cycloaraneosene derivative such as cycloaraneosene-
CC 8,9,13,19-tetraol (PubMed:27072286). Although the order of the
CC 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=GDP-alpha-D-mannose = GDP-4-dehydro-alpha-D-rhamnose + H2O;
CC Xref=Rhea:RHEA:23820, ChEBI:CHEBI:15377, ChEBI:CHEBI:57527,
CC ChEBI:CHEBI:57964; EC=4.2.1.47;
CC Evidence={ECO:0000250|UniProtKB:P93031};
CC -!- COFACTOR:
CC Name=NADP(+); Xref=ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P93031};
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000305|PubMed:27072286}.
CC -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC family. GDP-mannose 4,6-dehydratase subfamily. {ECO:0000305}.
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DR EMBL; LC079035; BAV32153.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1B4XBH2; -.
DR SMR; A0A1B4XBH2; -.
DR GO; GO:0008446; F:GDP-mannose 4,6-dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0042350; P:GDP-L-fucose biosynthetic process; IEA:UniProt.
DR GO; GO:0019673; P:GDP-mannose metabolic process; IEA:InterPro.
DR HAMAP; MF_00955; GDP_Man_dehydratase; 1.
DR InterPro; IPR006368; GDP_Man_deHydtase.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR PANTHER; PTHR43715; PTHR43715; 1.
DR Pfam; PF16363; GDP_Man_Dehyd; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01472; gmd; 1.
PE 3: Inferred from homology;
KW Antibiotic biosynthesis; Lyase; NADP.
FT CHAIN 1..544
FT /note="GDP-mannose 4,6-dehydratase sdnI"
FT /id="PRO_0000441060"
FT REGION 366..406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 135
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P93031"
FT ACT_SITE 157
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P93031"
FT BINDING 16..21
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P93031"
FT BINDING 41
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P93031"
FT BINDING 64..65
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P93031"
FT BINDING 86..90
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P93031"
FT BINDING 90
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P93031"
FT BINDING 157
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P93031"
FT BINDING 161
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P93031"
FT BINDING 186
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P93031"
FT BINDING 187
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P93031"
FT BINDING 192..200
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P93031"
FT BINDING 192
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P93031"
FT BINDING 219
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P93031"
FT BINDING 225
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P93031"
FT BINDING 303..306
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P93031"
SQ SEQUENCE 544 AA; 59012 MW; 53C3078D45D40D32 CRC64;
MATVDSQRPK SAFITGITGQ DGSYLVDILL EKGYQVHGLV RPSSQRRQFL SHPLRRGITL
HYGDMTDSAT LMQILSSITV DEVYHLAAQS HVAVSFQTPL LTCDINALGT LRLLEVLRIL
GLEKRVRFYS AVTSELFGNE APAPQTEETP MAPVSPYAVS KLFQYAITAN FREAYGFHAS
NGILFNHESP RRGTTFVTRK ITTQVALIAC GLSESFELGN LNATRDWGHA QDYMEGVWMM
LQQPEGSDYV LATGQASSVR DFVEAAFKVI GTKIEWSGEN ESEMGTEVGT GKVRVRVNPE
YYRPVENENL LGSAVKAKAA FGWEPKYTLE SLVEEMVLSD IELVKSGKMF STTNLDWLID
RSAEDGETTS AVNSSPSSTA GDTYKASDGW STSGAEGSEQ TECSSVAEGT DIPVPEKVEL
LPSAGVEEGG HDVAIDVLGK DDCGKVVLTL DEQDKPNEND EGHLAVVAVE EATATTPFVG
TDLIKMDSSI SIEPATPSPS TVAESERRVN LTITIDGEGR VTKVYNVPDF TAEEKVTLPT
PVTA
