ID   ICCD_TALVA              Reviewed;         292 AA.
AC   A0A482NB13;
DT   26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT   05-JUN-2019, sequence version 1.
DT   03-AUG-2022, entry version 9.
DE   RecName: Full=S-adenosyl-L-methionine-dependent Diels-Alderase iccD {ECO:0000303|PubMed:30905148};
DE            EC=2.1.-.- {ECO:0000269|PubMed:30905148};
DE   AltName: Full=C-methyltransferase iccD {ECO:0000303|PubMed:30905148};
DE            Short=C-MT iccD {ECO:0000303|PubMed:30905148};
DE   AltName: Full=Ilicicolin H biosynthesis cluster protein D {ECO:0000303|PubMed:30905148};
DE   AltName: Full=Pericyclase iccD {ECO:0000303|PubMed:30905148};
GN   Name=iccD {ECO:0000303|PubMed:30905148};
OS   Talaromyces variabilis (Penicillium variabile).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces.
OX   NCBI_TaxID=28576;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RC   STRAIN=HXQ-H-1;
RX   PubMed=30905148; DOI=10.1021/jacs.9b02204;
RA   Zhang Z., Jamieson C.S., Zhao Y.L., Li D., Ohashi M., Houk K.N., Tang Y.;
RT   "Enzyme-catalyzed inverse-electron demand Diels-Alder reaction in the
RT   biosynthesis of antifungal ilicicolin H.";
RL   J. Am. Chem. Soc. 141:5659-5663(2019).
CC   -!- FUNCTION: S-adenosyl-l-methionine-dependent Diels-Alderase; part of the
CC       gene cluster that mediates the biosynthesis of ilicicolin H, a 4-
CC       hydroxy-2-pyridonealkaloid that has potent and broad antifungal
CC       activities by inhibiting the mitochondrial respiration chain
CC       (PubMed:30905148). IccD catalyzes the Diels-Alder reaction that
CC       converts the acyclic 2-pyridone intermediate to 8-epi-ilicicolin H
CC       (PubMed:30905148). The biosynthesis of ilicicolin H starts with
CC       formation of the tetramic acid by the hybrid PKS-NRPS synthetase iccA
CC       with the partnering trans-enoyl reductase iccB since iccA lacks a
CC       designated enoylreductase (ER) domain. The cytochrome P450
CC       monooxygenase iccC then catalyzes the ring expansion of the tetramate
CC       to the acyclic 2-pyridone. The pericyclase iccD further converts the
CC       acyclic 2-pyridone into 8-epi-ilicicolin H. Finally, the epimerase iccE
CC       converts 8-epi-ilicicolin H into ilicicolin H via epimerization. IccA
CC       to iccE are sufficient for ilicicolin H biosynthesis and the roles of
CC       the remaining enzymes, iccF, iccG and iccH within the pathway have
CC       still to be determined (PubMed:30905148) (Probable).
CC       {ECO:0000269|PubMed:30905148, ECO:0000305|PubMed:30905148}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3-[(2E,4E,8S,10E,12Z)-4,8-dimethyltetradeca-2,4,10,12-
CC         tetraenoyl]-4-hydroxy-5-(4-hydroxyphenyl)-1,2-dihydropyridin-2-one =
CC         8-epi-ilicicolin H; Xref=Rhea:RHEA:64556, ChEBI:CHEBI:155888,
CC         ChEBI:CHEBI:155889; Evidence={ECO:0000269|PubMed:30905148};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64557;
CC         Evidence={ECO:0000269|PubMed:30905148};
CC   -!- COFACTOR:
CC       Name=S-adenosyl-L-methionine; Xref=ChEBI:CHEBI:59789;
CC         Evidence={ECO:0000305|PubMed:30905148};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=54 uM for the acyclic 2-pyridone {ECO:0000269|PubMed:30905148};
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:30905148}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC       superfamily. Erg6/SMT family. {ECO:0000305}.
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DR   EMBL; MK539848; QBQ83708.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A482NB13; -.
DR   SMR; A0A482NB13; -.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0008168; F:methyltransferase activity; IEA:InterPro.
DR   Gene3D; 3.40.50.150; -; 1.
DR   InterPro; IPR013216; Methyltransf_11.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   Pfam; PF08241; Methyltransf_11; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
PE   1: Evidence at protein level;
KW   Membrane; Transferase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..292
FT                   /note="S-adenosyl-L-methionine-dependent Diels-Alderase
FT                   iccD"
FT                   /id="PRO_0000449008"
FT   TRANSMEM        240..262
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   292 AA;  32714 MW;  D45BF7BDAE522E6A CRC64;
     MASSEVFTSE EAAQRAIKTY YESQESRMGY ELVFGGTQHF GYYTPGTWSP FPIDKSLRRM
     EEKLMGWLAL PAGSRILEAG CGVGHVALYL AKHGMRVTGV DIIDHHVEQA RRSAQKANLP
     KDQIVIEKMD FERLEAIPSA SHDGAFTMQS LGHAFSAEKA LAGFFRVLKP GGRFALVEVE
     RRPNAEADKK NPRLTEQLSM INVGTGMPTN ERSHDGFYKG LLEEAGFVDI ESRDISDNIL
     PVVRMFYVVL LVPYLFVRLL GIEKHFVSML AGTAGYVGYD RWRFMVVTGR KP