ICCB_TALVA
ID ICCB_TALVA Reviewed; 375 AA.
AC A0A482N9T9;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 05-JUN-2019, sequence version 1.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=Trans-enoyl reductase iccB {ECO:0000303|PubMed:30905148};
DE EC=1.-.-.- {ECO:0000269|PubMed:30905148};
DE AltName: Full=Ilicicolin H biosynthesis cluster protein B {ECO:0000303|PubMed:30905148};
GN Name=iccB {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, AND
RP 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: Trans-enoyl reductase; part of the gene cluster that mediates
CC the biosynthesis of ilicicolin H, a 4-hydroxy-2-pyridonealkaloid that
CC has potent and broad antifungal activities by inhibiting the
CC mitochondrial respiration chain (PubMed:30905148). IccB collaborates
CC with the hybrid PKS-NRPS synthetase iccA to assemble the backbone of
CC ilicicolin H (PubMed:30905148). The PKS portion of iccA and trans-
CC acting enoyl reductase iccB work together to construct an octaketide,
CC and two methyl groups are introduced by the MT domain of iccA during
CC the chain assembly (PubMed:30905148). The nascent chain is then
CC condensed with tyrosine, catalyzed by the iliA C domain, and the
CC resulting PKS-NRPS hybrid is offloaded by the iliA RED domain to form
CC an advanced tetramic acid intermediate (PubMed:30905148). The
CC biosynthesis of ilicicolin H starts with formation of the tetramic acid
CC by the hybrid PKS-NRPS synthetase iccA with the partnering trans-enoyl
CC reductase iccB since iccA lacks a designated enoylreductase (ER)
CC domain. The cytochrome P450 monooxygenase iccC then catalyzes the ring
CC expansion of the tetramate to the acyclic 2-pyridone. The pericyclase
CC iccD further converts the acyclic 2-pyridone into 8-epi-ilicicolin H.
CC Finally, the epimerase iccE converts 8-epi-ilicicolin H into ilicicolin
CC H via epimerization. IccA to iccE are sufficient for ilicicolin H
CC biosynthesis and the roles of the remaining enzymes, iccF, iccG and
CC iccH within the pathway have still to be determined (PubMed:30905148)
CC (Probable). {ECO:0000269|PubMed:30905148, ECO:0000305|PubMed:30905148}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-[(4E,6E,10S,12Z,14E)-6,10-dimethyl-3-oxohexadeca-4,6,12,14-
CC tetraenoyl]-L-tyrosyl-[ACP] = (3E,5S)-3-[(2E,4E,8S,10E,12Z)-1-
CC hydroxy-4,8-dimethyltetradeca-2,4,10,12-tetraen-1-ylidene]-5-[(4-
CC hydroxyphenyl)methyl]pyrrolidine-2,4-dione + H(+) + holo-[ACP];
CC Xref=Rhea:RHEA:64548, Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:16623,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:64479, ChEBI:CHEBI:155890,
CC ChEBI:CHEBI:155893; Evidence={ECO:0000269|PubMed:30905148};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64549;
CC Evidence={ECO:0000269|PubMed:30905148};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:30905148}.
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; MK539848; QBQ83710.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A482N9T9; -.
DR SMR; A0A482N9T9; -.
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.
FT CHAIN 1..375
FT /note="Trans-enoyl reductase iccB"
FT /id="PRO_0000449007"
FT BINDING 48..51
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 143..150
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 204..207
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 222
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 269..270
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 289..293
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 358..359
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 375 AA; 39426 MW; 5FDE2C309AEF1496 CRC64;
MDATLPSIHT ALKILGPNNV SVSENTALPV IQPLDILVRV ACISINHVDA KSADMSPSPG
ATSGTDFSGV VVAIGSDVPK ESFRSTNGMK PVQIGDRVFG GVFGNNPLRR DNGAFAEYVA
VPARLVWHIP GGMDFSTAST LGAAVATVGL SLFQYMQLPM PTTTSTASPD NGPFVLVYGG
GTATGAMAIQ VLKIAGFRPI TTCSSASAGH ATELGATATF DYRSPTCGAE LREHTGDTLT
LALDCITDTA SMNICYEALG SSGGRYVALD SFPLRAHTRR SVVPDWVCTY SQFGHPIAWA
APYNLEARPE DLLTAEAWYV VAQKLIDQGL ITPHPKEERL GGLAAIGEGM EAVRRGQIKG
KKLVYPISNE LCAAA
