ID   HIMF_ASPJA              Reviewed;         331 AA.
AC   A0A2Z5TWF0;
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=NmrA-like family domain-containing oxidoreductase himF {ECO:0000303|PubMed:29314577};
DE            EC=1.-.-.- {ECO:0000305|PubMed:29314577};
DE   AltName: Full=Himeic acid A biosynthesis cluster protein F {ECO:0000303|PubMed:29314577};
GN   Name=himF {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: NmrA-like family domain-containing oxidoreductase; part of
CC       the him gene cluster that mediates the biosynthesis of himeic acid A, a
CC       ubiquitin-activating enzyme (E1) inhibitor (PubMed:29314577). First,
CC       himA, together with the trans-enoyl reductase himH, catalyzes the
CC       formation of apolyketide chain, which is then condensed with leucine by
CC       the NRPS activity of himA. Dieckmann cyclization and release from himA
CC       gives a tetramic acid intermediate as the product of himA PKS-NRPS
CC       (PubMed:29314577). HimG then catalyzes alpha-oxidation of the tetramic
CC       acid ring, with a subsequent rearrangement to yield apyrone
CC       intermediate (Probable). Two terminal methyl groups of polyketide and
CC       amide side chains are oxidized to carboxylic acids by himC cytochrome
CC       P450 monooxygenase to form himeic acid A (Probable). Himeic acid A is
CC       further converted to himeic acid B and C during culture growth. No gene
CC       responsible for pyrone to pyridone conversion was found in the him gene
CC       cluster and himeic acid A is non-enzymatically converted to himeic acid
CC       C by the incorporation of an ammonium nitrogen atom in a pH5 buffer,
CC       and to himeic acid B at a conversion ratio of 50% during incubation in
CC       MeOH for 5 days (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   -!- SIMILARITY: Belongs to the NmrA-type oxidoreductase family.
CC       {ECO:0000305}.
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DR   EMBL; LC331673; BBA91554.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A2Z5TWF0; -.
DR   SMR; A0A2Z5TWF0; -.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR008030; NmrA-like.
DR   Pfam; PF05368; NmrA; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   3: Inferred from homology;
KW   NADP; Oxidoreductase.
FT   CHAIN           1..331
FT                   /note="NmrA-like family domain-containing oxidoreductase
FT                   himF"
FT                   /id="PRO_0000445954"
FT   BINDING         8..13
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9HBL8"
FT   BINDING         34..38
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9HBL8"
FT   BINDING         55..56
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9HBL8"
FT   BINDING         76..78
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9HBL8"
FT   BINDING         133
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9HBL8"
FT   BINDING         155..167
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9HBL8"
SQ   SEQUENCE   331 AA;  35903 MW;  03C9C7BE1555D7E9 CRC64;
     MQIITIFGAT GNQGSSVARS LLRNRSFEVR CITRNAESKK AQLLKAQGAV IVEADGYDTS
     QIQQAFSGSW GAFVNTNGDD PSLASENRTD RDLGLSIIRG AAAAGVKHLV YSSGPWAAKL
     SGGACSVPSN DAKAEVQHVA QGLGFETVTP IMPGWFFETF LEPQMAAIFG GFPVTPDEEG
     WLTCRAPLWG GREHVPFLSV DNDFGDIVHG VFLNPVRWNL RPIQAISDFL SFADFVNTYV
     SLTGKKARFV ALSSPMEMET MGHPLLESIR GFFIFSQLRD GEYFGTGPTE KETATALKQA
     AHRAQANDRK GEQAALTSAR DFLQARFGNS K