ID   HIMH_ASPJA              Reviewed;         342 AA.
AC   A0A2Z5TIQ0;
DT   05-DEC-2018, integrated into UniProtKB/Swiss-Prot.
DT   10-OCT-2018, sequence version 1.
DT   03-AUG-2022, entry version 8.
DE   RecName: Full=Trans-enoyl reductase himH {ECO:0000303|PubMed:29314577};
DE            EC=1.-.-.- {ECO:0000305|PubMed:29314577};
DE   AltName: Full=Himeic acid A biosynthesis cluster protein H {ECO:0000303|PubMed:29314577};
GN   Name=himH {ECO:0000303|PubMed:29314577};
OS   Aspergillus japonicus.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX   NCBI_TaxID=34381;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC   STRAIN=MF275;
RX   PubMed=29314577; DOI=10.1002/cbic.201700584;
RA   Hashimoto M., Kato H., Katsuki A., Tsukamoto S., Fujii I.;
RT   "Identification of the biosynthetic gene cluster for himeic acid A: a
RT   ubiquitin-activating enzyme (E1) inhibitor in Aspergillus japonicus
RT   MF275.";
RL   ChemBioChem 19:535-539(2018).
RN   [2]
RP   FUNCTION.
RX   PubMed=29486950; DOI=10.1016/j.bmc.2018.02.034;
RA   Katsuki A., Kato H., Tahara Y., Hashimoto M., Fujii I., Tsukamoto S.;
RT   "pH-dependent production of himeic acid A and its non-enzymatic conversions
RT   to himeic acids B and C.";
RL   Bioorg. Med. Chem. 26:1869-1874(2018).
CC   -!- FUNCTION: Trans-enoyl reductase; part of the him gene cluster that
CC       mediates the biosynthesis of himeic acid A, a ubiquitin-activating
CC       enzyme (E1) inhibitor (PubMed:29314577). First, himA, together with the
CC       trans-enoyl reductase himH, catalyzes the formation of apolyketide
CC       chain, which is then condensed with leucine by the NRPS activity of
CC       himA. Dieckmann cyclization and release from himA gives a tetramic acid
CC       intermediate as the product of himA PKS-NRPS (PubMed:29314577). HimG
CC       then catalyzes alpha-oxidation of the tetramic acid ring, with a
CC       subsequent rearrangement to yield apyrone intermediate (Probable). Two
CC       terminal methyl groups of polyketide and amide side chains are oxidized
CC       to carboxylic acids by himC cytochrome P450 monooxygenase to form
CC       himeic acid A (Probable). Himeic acid A is further converted to himeic
CC       acid B and C during culture growth. No gene responsible for pyrone to
CC       pyridone conversion was found in the him gene cluster and himeic acid A
CC       is non-enzymatically converted to himeic acid C by the incorporation of
CC       an ammonium nitrogen atom in a pH5 buffer, and to himeic acid B at a
CC       conversion ratio of 50% during incubation in MeOH for 5 days
CC       (PubMed:29486950). {ECO:0000269|PubMed:29314577,
CC       ECO:0000269|PubMed:29486950, ECO:0000305|PubMed:29314577}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:29314577}.
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; LC331673; BBA91552.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A2Z5TIQ0; -.
DR   SMR; A0A2Z5TIQ0; -.
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; IPR013154; ADH_N.
DR   InterPro; IPR011032; GroES-like_sf.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020843; PKS_ER.
DR   Pfam; PF08240; ADH_N; 1.
DR   Pfam; PF00107; ADH_zinc_N; 1.
DR   SMART; SM00829; PKS_ER; 1.
DR   SUPFAM; SSF50129; SSF50129; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   3: Inferred from homology;
KW   NADP; Nucleotide-binding; Oxidoreductase.
FT   CHAIN           1..342
FT                   /note="Trans-enoyl reductase himH"
FT                   /id="PRO_0000445956"
FT   BINDING         46..49
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT   BINDING         133..140
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255"
FT   BINDING         168..171
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT   BINDING         191..194
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT   BINDING         255..256
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT   BINDING         329..330
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ   SEQUENCE   342 AA;  36354 MW;  8A44EE628ED9B8D9 CRC64;
     MASLINQAAW QPKARTRSLQ VGPGPTPSPN EHEIVIKVAY AAVNPTDWKM QDTPYFELEY
     PFIWGTDVAG TIVQLGSEVT QFKVGQRVIG HCDSLLTRKV TNAGFQLYTT VREILVAEIP
     DSLPLANAAV LPLSVSTAAS ALYVQLDLPF PSLSPKSTGK RIVIWGGSSS VGSSAIQLAV
     ASGLEVVATA SQANHDLVRS LGASQVFDHR APSVIDQMAS VLQPGDYVVD CIGSPDTQAK
     CGELVGRIGG GTLPVMLWPQ GGLPQNVRAV FVNGLDPGMV NLDVGNAVWR KFIPEALAAG
     KFQAKPDPRI VPGGLEKVQE GIDMLRQGVS AQKIVIEISR SE