MYCB_MYCTT
ID MYCB_MYCTT Reviewed; 440 AA.
AC G2Q9A6;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 25-MAY-2022, entry version 27.
DE RecName: Full=Diels-Alderase mycB {ECO:0000303|PubMed:27960349};
DE EC=5.5.1.- {ECO:0000269|PubMed:27960349};
DE AltName: Full=Myceliothermophin biosynthesis cluster protein B {ECO:0000303|PubMed:27960349};
DE Flags: Precursor;
GN Name=mycB {ECO:0000303|PubMed:27960349}; ORFNames=MYCTH_114667;
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, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, 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: Diels-Alderase; part of the gene cluster that mediates the
CC biosynthesis of myceliothermophins, mycotoxins that contain a trans-
CC fused decalin ring system connected to a conjugated 3-pyrrolin-2-one
CC moiety and that have potential anti-tumor properties (PubMed:27960349).
CC The polyketide synthase module (PKS) of the PKS-NRPS mycA is
CC 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=(5S)-5-(2-methylpropyl)-3-[(2E,6R,8E,10E,12E)-6,8,10,12-
CC tetramethyltetradeca-2,8,10,12-tetraenoyl]-2,5-dihydro-1H-pyrrol-2-
CC one = (5S)-3-[(1S,2R,4aR,6R,8aS)-2-(but-2-en-2-yl)-3,4a,6-trimethyl-
CC 1,2,4a,5,6,7,8,8a-octahydronaphthalene-1-carbonyl]-5-(2-
CC methylpropyl)-2,5-dihydro-1H-pyrrol-2-one; Xref=Rhea:RHEA:67308,
CC ChEBI:CHEBI:169930, ChEBI:CHEBI:169934;
CC Evidence={ECO:0000269|PubMed:27960349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67309;
CC Evidence={ECO:0000269|PubMed:27960349};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z)-5-(2-methylpropylidene)-3-[(2E,6R,8E,10E,12E)-6,8,10,12-
CC tetramethyltetradeca-2,8,10,12-tetraenoyl]-2,5-dihydro-1H-pyrrol-2-
CC one = myceliothermophin E; Xref=Rhea:RHEA:67312, ChEBI:CHEBI:167709,
CC ChEBI:CHEBI:169932; Evidence={ECO:0000269|PubMed:27960349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67313;
CC Evidence={ECO:0000269|PubMed:27960349};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=75 uM for the C18 keto acyclic precursor
CC {ECO:0000269|PubMed:27960349};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:27960349}.
CC -!- DISRUPTION PHENOTYPE: Completely abolishes the production of
CC myceliothermophin E, but leads to the accumulation of its C18 keto
CC acyclic precursor. {ECO:0000269|PubMed:27960349}.
CC -!- SIMILARITY: Belongs to the Diels-Alderase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CP003003; AEO57198.1; -; Genomic_DNA.
DR RefSeq; XP_003662443.1; XM_003662395.1.
DR AlphaFoldDB; G2Q9A6; -.
DR SMR; G2Q9A6; -.
DR EnsemblFungi; AEO57198; AEO57198; MYCTH_114667.
DR GeneID; 11512496; -.
DR KEGG; mtm:MYCTH_114667; -.
DR VEuPathDB; FungiDB:MYCTH_114667; -.
DR eggNOG; ENOG502SK1F; Eukaryota.
DR HOGENOM; CLU_041924_1_0_1; -.
DR InParanoid; G2Q9A6; -.
DR OrthoDB; 1068172at2759; -.
DR Proteomes; UP000007322; Chromosome 2.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Glycoprotein; Isomerase; Reference proteome; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..440
FT /note="Diels-Alderase mycB"
FT /id="PRO_5003436058"
FT CARBOHYD 80
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 332
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 440 AA; 49347 MW; 5DC67D6456AD0FB3 CRC64;
MGYLVKLACG LLLPLATADV NLAQQPFGEF EWQPKFDTPS GDHTSCAVSR LSAYEVGEGP
VSFSLSPTEH PEIPKLSTIN STVWEQWEFD AVSESGTGSV LMGFSRDPSY SFFGQGNLRV
EFYMTLEDGT RIQELEYTES STVIDCPDSI RGIWNSSDRS YAFEISRDMQ RARVWWDTGR
EKGSIAIEST TTPHLADGEI WPPEEGESRV KKSWPSVKLS PGLYMSQPIA GGKVTAHVQI
GKKTMSITGY GAHSRLWAEN SWFKICRGWQ IMRGFLGPYT ISYWRPLSRL DDWVPYFAAH
LFKHGRLVFT SQVGAPSQQV DYTQFHSDFS GNVSGSLADK ATGRVLEFVS PSTGKTWRFH
HRHFAKMFEM GFGGGRGLTG FLDEIVGGEV GTDEEFTGRG FSEQVLLPDE IKQWQIWVVY
GIGFLGRWKN TVTNLVLSIW
