ID   PENJ_PENTH              Reviewed;         199 AA.
AC   A0A1B2CTB8;
DT   25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT   02-NOV-2016, sequence version 1.
DT   03-AUG-2022, entry version 12.
DE   RecName: Full=Epoxide hydrolase penJ {ECO:0000303|PubMed:25859931};
DE            EC=3.-.-.- {ECO:0000269|PubMed:25859931};
DE   AltName: Full=Penigequinolones biosynthesis cluster protein J {ECO:0000303|PubMed:25859931};
GN   Name=penJ {ECO:0000303|PubMed:25859931};
OS   Penicillium thymicola.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=293382;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP   PATHWAY.
RC   STRAIN=IBT 5891 / CBS 111225;
RX   PubMed=25859931; DOI=10.1021/jacs.5b03022;
RA   Zou Y., Zhan Z., Li D., Tang M., Cacho R.A., Watanabe K., Tang Y.;
RT   "Tandem prenyltransferases catalyze isoprenoid elongation and complexity
RT   generation in biosynthesis of quinolone alkaloids.";
RL   J. Am. Chem. Soc. 137:4980-4983(2015).
RN   [2]
RP   FUNCTION.
RX   PubMed=28114276; DOI=10.1038/nchembio.2283;
RA   Zou Y., Garcia-Borras M., Tang M.C., Hirayama Y., Li D.H., Li L.,
RA   Watanabe K., Houk K.N., Tang Y.;
RT   "Enzyme-catalyzed cationic epoxide rearrangements in quinolone alkaloid
RT   biosynthesis.";
RL   Nat. Chem. Biol. 13:325-332(2017).
CC   -!- FUNCTION: Epoxide hydrolase; part of the gene cluster that mediates the
CC       biosynthesis of penigequinolones, potent insecticidal alkaloids that
CC       contain a highly modified 10-carbon prenyl group (PubMed:25859931). The
CC       first stage is catalyzed by the nonribosomal pepdide synthetase penN
CC       that condenses anthranilic acid and O-methyl-L-tyrosine to produce 4'-
CC       methoxycyclopeptin (By similarity). 4'-methoxycyclopeptin is then
CC       converted to 4'-methoxydehydrocyclopeptin by the ketoglutarate-
CC       dependent dioxygenase penM through dehydrogenation to form a double
CC       bond between C-alpha and C-beta of the O-methyltyrosine side chain (By
CC       similarity). PenM also converts its first product
CC       methoxydehydrocyclopeptin to 4'-methoxycyclopenin (By similarity). The
CC       following conversion of 4'methoxycyclopenin into 4'-methoxyviridicatin
CC       is catalyzed by the cyclopenase penL (By similarity). 4'-
CC       methoxyviridicatin is the precursor of quinolone natural products, and
CC       is further converted to quinolinone B (Probable). The prenyltransferase
CC       penI then catalyzes the canonical Friedel-Crafts alkylation of
CC       quinolinone B with dimethylallyl cation to yield dimethylallyl
CC       quinolone, which is subjected to FAD-dependent dehydrogenation by the
CC       FAD-linked oxidoreductase penH to yield conjugated aryl diene
CC       (PubMed:25859931). The delta(3') double bond then serves as the site of
CC       the second alkylation with DMAPP catalyzed by the prenyltransferase
CC       penG to yield a carbenium ion intermediate, which can be attacked by
CC       H(2)O to yield a styrenyl quinolone containing a C3'-hydroxyprenyl
CC       chain, or undergo cyclization to yield yaequinolones J1 and J2
CC       (PubMed:25859931). The conversion of the styrenyl quinolone into the
CC       tetrahydrofuran-containing yaequinolone C is performed by the FAD-
CC       dependent monooxygenase penE and involves epoxidation of the terminal
CC       C7'-C8' olefin, followed by epoxide ring opening initiated by the C3'
CC       hydroxyl group (PubMed:25859931). The predicted cysteine hydrolase penJ
CC       acts as an epoxide hydrolase that enhances the rate of the 5-exo-tet
CC       cyclization step, increasing the yield of yaequinolone C
CC       (PubMed:25859931, PubMed:28114276). PenF catalyzes the cationic
CC       rearrangement of the epoxide formed by penE (before ring opening to
CC       produce yaequinolone C) into yaequinolone D (PubMed:28114276). Finally,
CC       the short-chain dehydrogenase/reductase (SDR)-like reductase penD,
CC       catalyzes both the dehydration of yaequinolone D and the reduction of
CC       the resulting oxonium to yield penigequinolone (PubMed:28114276).
CC       {ECO:0000250|UniProtKB:C8VJQ3, ECO:0000250|UniProtKB:Q5AR53,
CC       ECO:0000250|UniProtKB:Q5AR54, ECO:0000269|PubMed:25859931,
CC       ECO:0000269|PubMed:28114276, ECO:0000305|PubMed:25859931}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:25859931}.
CC   -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:25859931}.
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:25859931}.
CC   -!- SIMILARITY: Belongs to the isochorismatase family. {ECO:0000305}.
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DR   EMBL; KX528209; ANY57888.1; -; Genomic_DNA.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.850; -; 1.
DR   InterPro; IPR000868; Isochorismatase-like.
DR   InterPro; IPR036380; Isochorismatase-like_sf.
DR   Pfam; PF00857; Isochorismatase; 1.
DR   SUPFAM; SSF52499; SSF52499; 1.
PE   1: Evidence at protein level;
KW   Hydrolase.
FT   CHAIN           1..199
FT                   /note="Epoxide hydrolase penJ"
FT                   /id="PRO_0000455363"
FT   ACT_SITE        30
FT                   /evidence="ECO:0000250|UniProtKB:G2X4M1"
FT   ACT_SITE        106
FT                   /evidence="ECO:0000250|UniProtKB:G2X4M1"
FT   ACT_SITE        141
FT                   /evidence="ECO:0000250|UniProtKB:G2X4M1"
SQ   SEQUENCE   199 AA;  21263 MW;  81B9A372FEF04984 CRC64;
     MSSTAQSFRE IVGIPRSSAS TQDSTLIIID AQNEYATGAL KVENVTETRK SIAKLLERYR
     QAGNGKNIVH VVHKVPEGAA VFTPNTPLAQ EFEELTPNTG EKVVTKNFPS SFAKTDLHTY
     LQGLGDVGKK VVLVGYMAHV CVSTTTRAAA ELGYDVLVVG DAVGDRDIPG VKVETLVSVV
     LSELADGFAT VVSEEDIRA