ID   ICCE_TALVA              Reviewed;         414 AA.
AC   A0A482N8M8;
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=NADH-dependent flavin oxidoreductase iccE {ECO:0000303|PubMed:30905148};
DE            EC=1.-.-.- {ECO:0000269|PubMed:30905148};
DE   AltName: Full=Epimerase iliE {ECO:0000303|PubMed:30905148};
DE   AltName: Full=Ilicicolin H biosynthesis cluster protein E {ECO:0000303|PubMed:30905148};
GN   Name=iccE {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: NADH-dependent flavin oxidoreductase; part of the gene
CC       cluster that mediates the biosynthesis of ilicicolin H, a 4-hydroxy-2-
CC       pyridonealkaloid that has potent and broad antifungal activities by
CC       inhibiting the mitochondrial respiration chain (PubMed:30905148). IccE
CC       acts as an epimerase and catalyzes the conversion of 8-epi-ilicicolin H
CC       into the final product ilicicolin H (PubMed:30905148). The biosynthesis
CC       of ilicicolin H starts with formation of the tetramic acid by the
CC       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=8-epi-ilicicolin H = ilicicolin H; Xref=Rhea:RHEA:64564,
CC         ChEBI:CHEBI:77772, ChEBI:CHEBI:155888;
CC         Evidence={ECO:0000269|PubMed:30905148};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64565;
CC         Evidence={ECO:0000269|PubMed:30905148};
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:30905148}.
CC   -!- SIMILARITY: Belongs to the NADH:flavin oxidoreductase/NADH oxidase
CC       family. {ECO:0000305}.
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DR   EMBL; MK539848; QBQ83707.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A482N8M8; -.
DR   SMR; A0A482N8M8; -.
DR   GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.20.20.70; -; 1.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR001155; OxRdtase_FMN_N.
DR   Pfam; PF00724; Oxidored_FMN; 1.
PE   1: Evidence at protein level;
KW   Flavoprotein; FMN; NADP; Oxidoreductase.
FT   CHAIN           1..414
FT                   /note="NADH-dependent flavin oxidoreductase iccE"
FT                   /id="PRO_0000449009"
FT   BINDING         25..28
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:P54550"
FT   BINDING         107
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:P54550"
FT   BINDING         188..191
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P54550"
FT   BINDING         347..348
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:P54550"
SQ   SEQUENCE   414 AA;  44593 MW;  40A328191E224456 CRC64;
     MADLHLAKSI TLRCGLTLPN RLAKTAIAES IAPRNMLIDE GFHRVYAPWA EGGWGMVLTG
     HVQVDSMHLG THTDPAVNAD FSDDQIVGSW KVWAAVCNRH GTPTIMQLNH PGRQAPIGAG
     TSGVFAKNIS ASAVPMDIGS GLLARAVSKI VFGTPREMTV DDIGKLVRQF ARAARLASQS
     GFAGVELHAS HGYLLAQFLS AATNRRKDAY GGTPANRARI VVEIIKAVRA EVPASFCVGI
     ILTAVHGSAS TEEFQSFIEQ AQLICDAGVD FIEISGGTFE TPSMFIGPEK RGKAYDWDNQ
     EAFFLDFAQA IRPHLGTVPL LLTGGFRSCH AMEAAVKRGD CDMIGLARPA VVNPLLPKTV
     VFNPEVNKSG DTKLHATRTP APWYIKLFGI TALNVHMDNA WYVGRLQTLA KTGR