ID   OPAE_ASPUT              Reviewed;         274 AA.
AC   A0A0C1EFK1;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-2015, sequence version 1.
DT   25-MAY-2022, entry version 15.
DE   RecName: Full=Epimerase opaE {ECO:0000303|PubMed:33004788};
DE            EC=5.1.-.- {ECO:0000269|PubMed:33004788};
DE   AltName: Full=Oxepinamide F biosynthesis cluster protein E {ECO:0000303|PubMed:33004788};
GN   Name=opaE {ECO:0000303|PubMed:33004788}; ORFNames=HK57_00061;
OS   Aspergillus ustus.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX   NCBI_TaxID=40382;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND IDENTIFICATION.
RC   STRAIN=3.3904;
RX   PubMed=25706180; DOI=10.1371/journal.pone.0116089;
RA   Pi B., Yu D., Dai F., Song X., Zhu C., Li H., Yu Y.;
RT   "A genomics based discovery of secondary metabolite biosynthetic gene
RT   clusters in Aspergillus ustus.";
RL   PLoS ONE 10:e0116089-e0116089(2015).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, DISRUPTION
RP   PHENOTYPE, AND PATHWAY.
RX   PubMed=33004788; DOI=10.1038/s41467-020-18713-0;
RA   Zheng L., Wang H., Fan A., Li S.M.;
RT   "Oxepinamide F biosynthesis involves enzymatic D-aminoacyl epimerization,
RT   3H-oxepin formation, and hydroxylation induced double bond migration.";
RL   Nat. Commun. 11:4914-4914(2020).
CC   -!- FUNCTION: Epimerase; part of the gene cluster that mediates the
CC       biosynthesis of oxepinamides, derivatives of anthranilyl-containing
CC       tripeptides that share an oxepin ring and a fused pyrimidinone moiety
CC       (PubMed:33004788). The nonribosomal peptide synthetase (NRPS) opaA
CC       assembles the quinazolinone core with D-Phe incorporation
CC       (PubMed:33004788). The first adenylation domain (A1) of opaA loads and
CC       activates anthranilic acid whereas the second A domain (A2) is for
CC       activating of L-Phe, which is then converted to D-form by the E domain
CC       (PubMed:33004788). The third A domain (A3) is responsible for L-Ile
CC       activation and the terminal condensation domain C3 for cyclization and
CC       releasing the NRPS product protuboxepin K (PubMed:33004788). The
CC       cytochrome P450 monooxygenase opaB then catalyzes alone the oxepin ring
CC       formation to convert protuboxepin K into protuboxepin A
CC       (PubMed:33004788). The flavoenzyme opaC installs subsequently one
CC       hydroxyl group at the oxepin ring, accompanied by double bond
CC       migration, to form 15-epi-oxepinamide E (PubMed:33004788). The
CC       epimerase opaE changes the D-Phe residue back to L-form, leading to
CC       oxepinamide E, which is further methylated at the hydroxyl group at C-
CC       12 by the O-methyltransferase OpaF to yield oxepinamide F
CC       (PubMed:33004788). {ECO:0000269|PubMed:33004788}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1.41 mM for 15-epi-oxepinamide E {ECO:0000269|PubMed:33004788};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:33004788}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of both oxepinamide F
CC       and oxepinamide E and leads to the accumulation of protuboxepin K.
CC       {ECO:0000269|PubMed:33004788}.
CC   -!- SIMILARITY: Belongs to the HyuE racemase family. {ECO:0000305}.
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DR   EMBL; JOMC01000153; KIA75454.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A0C1EFK1; -.
DR   SMR; A0A0C1EFK1; -.
DR   EnsemblFungi; KIA75454; KIA75454; HK57_00061.
DR   Proteomes; UP000053475; Unassembled WGS sequence.
DR   GO; GO:0036361; F:racemase activity, acting on amino acids and derivatives; IEA:InterPro.
DR   GO; GO:0006807; P:nitrogen compound metabolic process; IEA:InterPro.
DR   InterPro; IPR015942; Asp/Glu/hydantoin_racemase.
DR   Pfam; PF01177; Asp_Glu_race; 1.
PE   1: Evidence at protein level;
KW   Isomerase; Reference proteome.
FT   CHAIN           1..274
FT                   /note="Epimerase opaE"
FT                   /id="PRO_0000452997"
FT   SITE            90
FT                   /note="Seems to be responsible for recognition and proton
FT                   retrieval of D-isomers"
FT                   /evidence="ECO:0000250|UniProtKB:Q6TMG4"
SQ   SEQUENCE   274 AA;  29551 MW;  FAA94FD69C718BA5 CRC64;
     MGPLRVFTDN KVKVMLLNPI GGAGFNDFVV ETVLNHKDPS THVTITSLAN RIGGNQTLAY
     PSIRPLLYGE MIRVCLQARK ENYDVLIINC FGDPMVDELQ QIAGDDMVIL GARQVAVQTA
     SKISSKYAVL LPYDMKSSPD PLHQRVVADT RTAVAHPVVD MAFNDDLTPM DGESLGERLA
     TQGKLAIKEN GAEVLVLGCT AMVGCWQGLM RAVGVPVIDP TVAALRAAGK AGRLKRELVG
     GASTKRSGTF PTEKELKMIA ESEPSYPFSG RIEI