MYCC_MYCTT
ID MYCC_MYCTT Reviewed; 371 AA.
AC G2Q9A7;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Trans-enoyl reductase mycC {ECO:0000303|PubMed:27960349};
DE EC=1.-.-.- {ECO:0000269|PubMed:27960349};
DE AltName: Full=Myceliothermophin biosynthesis cluster protein C {ECO:0000303|PubMed:27960349};
GN Name=mycC {ECO:0000303|PubMed:27960349}; ORFNames=MYCTH_114666;
OS Myceliophthora thermophila (strain ATCC 42464 / BCRC 31852 / DSM 1799)
OS (Sporotrichum thermophile).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Chaetomiaceae; Thermothelomyces.
OX NCBI_TaxID=573729;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 42464 / BCRC 31852 / DSM 1799;
RX PubMed=21964414; DOI=10.1038/nbt.1976;
RA Berka R.M., Grigoriev I.V., Otillar R., Salamov A., Grimwood J., Reid I.,
RA Ishmael N., John T., Darmond C., Moisan M.-C., Henrissat B., Coutinho P.M.,
RA Lombard V., Natvig D.O., Lindquist E., Schmutz J., Lucas S., Harris P.,
RA Powlowski J., Bellemare A., Taylor D., Butler G., de Vries R.P.,
RA Allijn I.E., van den Brink J., Ushinsky S., Storms R., Powell A.J.,
RA Paulsen I.T., Elbourne L.D.H., Baker S.E., Magnuson J., LaBoissiere S.,
RA Clutterbuck A.J., Martinez D., Wogulis M., de Leon A.L., Rey M.W.,
RA Tsang A.;
RT "Comparative genomic analysis of the thermophilic biomass-degrading fungi
RT Myceliophthora thermophila and Thielavia terrestris.";
RL Nat. Biotechnol. 29:922-927(2011).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=27960349; DOI=10.1021/jacs.6b10452;
RA Li L., Yu P., Tang M.C., Zou Y., Gao S.S., Hung Y.S., Zhao M., Watanabe K.,
RA Houk K.N., Tang Y.;
RT "Biochemical characterization of a eukaryotic decalin-forming Diels-
RT Alderase.";
RL J. Am. Chem. Soc. 138:15837-15840(2016).
CC -!- FUNCTION: Trans-enoyl reductase; part of the gene cluster that mediates
CC the biosynthesis of myceliothermophins, mycotoxins that contain a
CC trans-fused decalin ring system connected to a conjugated 3-pyrrolin-2-
CC one moiety and that have potential anti-tumor properties
CC (PubMed:27960349). The polyketide synthase module (PKS) of the PKS-NRPS
CC mycA is responsible for the synthesis of the octaketide backbone
CC (PubMed:27960349). The downstream nonribosomal peptide synthetase
CC (NRPS) module then amidates the carboxyl end of the octaketide with a
CC leucine (PubMed:27960349). A reductase-like domain (R) at the C-
CC terminus catalyzes the reductive release of the polyketide-amino acid
CC intermediate (PubMed:27960349). Because mycA lacks a designated
CC enoylreductase (ER) domain, the required activity is provided the enoyl
CC reductase mycC (PubMed:27960349). Following mycA-catalyzed construction
CC and release of aminoacyl polyketide aldehyde, Knoevenagel condensation
CC yields the expected ketone (PubMed:27960349). This C18 keto acyclic
CC precursor is the substrate of the Diels-Alderase mycB, that catalyzes
CC the Diels-Alder cycloaddition to produce myceliothermophin E
CC (PubMed:27960349). A yet unknown oxygenase involved in the production
CC of myceliothermophin A, via substitution with a hydroxyl group at the
CC C21, has still to be identified (PubMed:27960349).
CC {ECO:0000269|PubMed:27960349}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + 12 H(+) + L-leucine + 8 malonyl-CoA + 9 NADPH + 4 S-
CC adenosyl-L-methionine = (5S)-5-(2-methylpropyl)-3-
CC [(2E,6R,8E,10E,12E)-6,8,10,12-tetramethyltetradeca-2,8,10,12-
CC tetraenoyl]-2,5-dihydro-1H-pyrrol-2-one + AMP + 8 CO2 + 8 CoA +
CC diphosphate + 7 H2O + 9 NADP(+) + 4 S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:67288, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:57427,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:57856, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:169930, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:27960349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67289;
CC Evidence={ECO:0000269|PubMed:27960349};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:27960349}.
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; CP003003; AEO57199.1; -; Genomic_DNA.
DR RefSeq; XP_003662444.1; XM_003662396.1.
DR AlphaFoldDB; G2Q9A7; -.
DR SMR; G2Q9A7; -.
DR STRING; 78579.XP_003662444.1; -.
DR EnsemblFungi; AEO57199; AEO57199; MYCTH_114666.
DR GeneID; 11512497; -.
DR KEGG; mtm:MYCTH_114666; -.
DR VEuPathDB; FungiDB:MYCTH_114666; -.
DR eggNOG; KOG1198; Eukaryota.
DR HOGENOM; CLU_026673_16_1_1; -.
DR InParanoid; G2Q9A7; -.
DR OrthoDB; 727365at2759; -.
DR Proteomes; UP000007322; Chromosome 2.
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..371
FT /note="Trans-enoyl reductase mycC"
FT /id="PRO_0000450501"
FT BINDING 51..54
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 140..147
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 182..185
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 205..208
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 223
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 270..271
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 291..295
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 361..362
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 371 AA; 40045 MW; 992666FE9C7DCDBB CRC64;
MAIDEQIPRV QRALIQSSTP GVLQFTETRE VPKLLPDQVL VRVVAVALNP CDWKMPTNFP
CPGAGVGADF SGTVVRVGDD VRPGKFDVKL GDRVAGAVHA SNRLKPQDGT FAEYIAVRAD
ALWRIPDGMD FHVAAAIGLC VVGTVGLAAF HERHLNLPGS PEQPVKPRAG GQPPWVLVYG
GSTASGTMAI QILKLAGFRV VTTCSPANFA LVESYGADKA FDYHSPNLGE SIRAYTNNSL
SFVMDIIASA NSLRQCYASI GRAGGHYVGF ELVPDELAGI RKAVRASWVL GIRLLGYEIA
LDRGYGSPPD PELGMWGRAW FKRTEDLVWG GKIRPHPIEL DTESGFDGIV AGVERLKRGE
VSGKKLVYLI R
