CGHC_CHAGB
ID CGHC_CHAGB Reviewed; 375 AA.
AC Q2HBN4;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=Trans-enoyl reductase cghC {ECO:0000303|PubMed:26360642};
DE Short=ER cghC {ECO:0000303|PubMed:26360642};
DE EC=1.-.-.- {ECO:0000269|PubMed:26360642};
DE AltName: Full=Sch210972 biosynthesis cluster protein C {ECO:0000303|PubMed:26360642};
GN Name=cghC {ECO:0000303|PubMed:26360642}; ORFNames=CHGG_02370;
OS Chaetomium globosum (strain ATCC 6205 / CBS 148.51 / DSM 1962 / NBRC 6347 /
OS NRRL 1970) (Soil fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Chaetomiaceae; Chaetomium.
OX NCBI_TaxID=306901;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 6205 / CBS 148.51 / DSM 1962 / NBRC 6347 / NRRL 1970;
RX PubMed=25720678; DOI=10.1128/genomea.00021-15;
RA Cuomo C.A., Untereiner W.A., Ma L.-J., Grabherr M., Birren B.W.;
RT "Draft genome sequence of the cellulolytic fungus Chaetomium globosum.";
RL Genome Announc. 3:E0002115-E0002115(2015).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=26360642; DOI=10.1002/cbic.201500386;
RA Sato M., Yagishita F., Mino T., Uchiyama N., Patel A., Chooi Y.H., Goda Y.,
RA Xu W., Noguchi H., Yamamoto T., Hotta K., Houk K.N., Tang Y., Watanabe K.;
RT "Involvement of lipocalin-like CghA in decalin-forming stereoselective
RT intramolecular [4+2] cycloaddition.";
RL ChemBioChem 16:2294-2298(2015).
CC -!- FUNCTION: Trans-enoyl reductase; part of the gene cluster that mediates
CC the biosynthesis of the tetramic acid Sch210972, a potential anti-HIV
CC fungal natural product that contains a decalin core (PubMed:26360642).
CC The PKS module of cghG together with the enoylreductase cghC catalyze
CC the formation of the polyketide unit which is then conjugated to 4-
CC hydroxyl-4-methyl glutamate (HMG) by the condensation domain of the
CC cghG NRPS module (PubMed:26360642). One unique structural feature of
CC Sch210972 is the tetramic acid motif proposed to be derived from the
CC non-proteinogenic amino acid HMG, by a Dieckmann-type condensation
CC catalyzed by the reductase domain of cghG (PubMed:26360642). The
CC aldolase cghB catalyzes the aldol condensation of 2 molecules of
CC pyruvic acid to yield the intermediate 4-hydroxyl-4-methyl-2-
CC oxoglutarate (HMOG), which can then be stereoselectively transaminated
CC by an unidentified enzyme to form HMG (PubMed:26360642). The Diels-
CC Alderase cghA then uses the Dieckmann product released by cghG as
CC substrate and catalyzes the Diels-Alder cycloaddition to form the
CC decalin ring of Sch210972 (PubMed:26360642). CghA also suppresses the
CC nonenzymatic formation of the alternative stereoisomer
CC (PubMed:26360642). {ECO:0000269|PubMed:26360642}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S,4S)-4-hydroxy-4-methylglutamate + ATP + 11 H(+) + 8
CC malonyl-CoA + 8 NADPH + 3 S-adenosyl-L-methionine = (2S)-3-[(2S)-3,5-
CC dioxo-4-[(2E,4R,6R,8E,10E,12E)-4,6,12-trimethyltetradeca-2,8,10,12-
CC tetraenoyl]pyrrolidin-2-yl]-2-hydroxy-2-methylpropanoate + AMP + 8
CC CO2 + 8 CoA + diphosphate + 6 H2O + 8 NADP(+) + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:67264, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:57856, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:167901, ChEBI:CHEBI:167907,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:26360642};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67265;
CC Evidence={ECO:0000269|PubMed:26360642};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:26360642}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9Y7D0}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; CH408030; EAQ90435.1; -; Genomic_DNA.
DR RefSeq; XP_001228886.1; XM_001228885.1.
DR SMR; Q2HBN4; -.
DR STRING; 38033.XP_001228886.1; -.
DR EnsemblFungi; EAQ90435; EAQ90435; CHGG_02370.
DR GeneID; 4388355; -.
DR eggNOG; KOG1198; Eukaryota.
DR HOGENOM; CLU_026673_16_1_1; -.
DR InParanoid; Q2HBN4; -.
DR OMA; AIMGMNP; -.
DR OrthoDB; 727365at2759; -.
DR Proteomes; UP000001056; Unassembled WGS sequence.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW NADP; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..375
FT /note="Trans-enoyl reductase cghC"
FT /id="PRO_0000453335"
FT BINDING 48..51
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 135..142
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 188..191
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 211..214
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 276..277
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 297..301
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 366..367
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 375 AA; 39772 MW; 82675B8CB12DAE76 CRC64;
MAISATTQSA LVGGSQDDII LSTSAPIPQR LEDDQVAVAV KAIALNPVDT KMLGDFHTPG
AVLGCEFSGV ITSAGPVATS EWGLREGDRV SGAIMGMNPL RPQIGAFAQH TVAPAHVVLK
VREDWDFAQG AGMGNAWYTS GWALFHTMGL PAGPQLEPLH TLVPPPPGNA GKLPSTNKPI
TVLVSGGSSS TGTTAVQLLK LAGYHVIATC SARNFDLARQ YGADEVFDHS SPTCAADIRE
RTRNALRFAL DCITTPETTR LCYAALGRSG GRYVSLDPFS EAVAATRGVV RPDWVLGPEL
VGEDIAWPEP HGRKGNPKAR VFCEAWTRTL QRLVDQGLVK THPQLVRDTG LKGALGGLDD
IRAKKVSGQK LVYLL
