ID   POXI_PENOX              Reviewed;         314 AA.
AC   A0A1W5T323;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2017, sequence version 1.
DT   03-AUG-2022, entry version 8.
DE   RecName: Full=Oxidoreductase poxI {ECO:0000303|PubMed:28365998};
DE            EC=1.3.1.- {ECO:0000305|PubMed:28365998};
DE   AltName: Full=Oxaleimides biosynthesis cluster protein I {ECO:0000303|PubMed:28365998};
GN   Name=poxI {ECO:0000303|PubMed:28365998};
OS   Penicillium oxalicum.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=69781;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, INDUCTION, AND PATHWAY.
RC   STRAIN=K85;
RX   PubMed=28365998; DOI=10.1021/jacs.7b02432;
RA   Sato M., Dander J.E., Sato C., Hung Y.S., Gao S.S., Tang M.C., Hang L.,
RA   Winter J.M., Garg N.K., Watanabe K., Tang Y.;
RT   "Collaborative Biosynthesis of Maleimide- and Succinimide-Containing
RT   Natural Products by Fungal Polyketide Megasynthases.";
RL   J. Am. Chem. Soc. 139:5317-5320(2017).
RN   [2]
RP   FUNCTION.
RX   PubMed=32039410; DOI=10.1039/c9cc09590j;
RA   Hantke V., Skellam E.J., Cox R.J.;
RT   "Evidence for enzyme catalysed intramolecular [4+2] Diels-Alder cyclization
RT   during the biosynthesis of pyrichalasin H.";
RL   Chem. Commun. (Camb.) 56:2925-2928(2020).
CC   -!- FUNCTION: Oxidoreductase; part of the gene cluster that mediates the
CC       biosynthesis of oxaleimides, cytotoxic compounds containing an unusual
CC       disubstituted succinimide moiety (PubMed:28365998). The first step of
CC       the pathway is provided by the HR-PKS poxF that serves in a new mode of
CC       collaborative biosynthesis with the PKS-NRPS poxE, by providing the
CC       olefin containing amino acid substrate via the synthesis of an ACP-
CC       bound dec-4-enoate (PubMed:28365998). The cytochrome P450 monooxygenase
CC       poxM-catalyzed oxidation at the alpha-position creates the enzyme-bound
CC       2-hydroxydec-4-enoyl-ACP thioester, which may be prone to spontaneous
CC       hydrolysis to yield 2-hydroxydec-4-enoic acid due to increased
CC       electrophilicity of the carbonyl (PubMed:28365998). 2-hydroxydec-4-
CC       enoic acid can then be further oxidized by poxM to yield the alpha-
CC       ketoacid 2-oxodec-4-enoicacid, which is reductively aminated by the
CC       aminotransferase poxL to yield (S,E)-2-aminodec-4-enoic acid
CC       (PubMed:28365998). The Hybrid PKS-NRPS synthetase poxE then performs
CC       condensation between the octaketide product of its PKS modules and the
CC       amino group of (S,E)-2-aminodec-4-enoic acid which is activated and
CC       incorporated by the adenylation domain (PubMed:28365998). The resulting
CC       aminoacyl product can be cyclized by the Diels-Alderase PoxQ and
CC       reductively released by the reductive (R) domain of poxE to yield an
CC       aldehyde intermediate (PubMed:28365998) (Probable). The released
CC       aldehyde is then substrate for a Knoevenagel condensation by the
CC       hydrolyase poxO followed by an oxidation at the 5-position of the
CC       pyrrolidone ring (PubMed:28365998). The presence of the olefin from the
CC       amino acid building block allows for migration of the substituted allyl
CC       group to occur (PubMed:28365998). This allylic transposition reaction
CC       takes place in a conjugate addition, semipinacol-like fashion to yield
CC       a succinimide intermediate (PubMed:28365998). Iterative two-electron
CC       oxidations of the C7 methyl of the succinimide intermediate to the
CC       carboxylic acid can be catalyzed by one of two remaining cytochrome
CC       P450 monooxygenasess poxC or poxD to yield oxaleimide A
CC       (PubMed:28365998). Subsequent oxidation yields the maleimide scaffold
CC       oxaleimide I (PubMed:28365998). Both oxaleimide A and oxaleimide I can
CC       undergo oxidative modifications in the decalin ring to yield the series
CC       of products oxaleimides B to H (PubMed:28365998).
CC       {ECO:0000269|PubMed:28365998, ECO:0000305|PubMed:32039410}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:28365998}.
CC   -!- INDUCTION: Expression is positively regulated by the oxaleimides
CC       biosynthesis cluster-specific transcription factor poxB.
CC       {ECO:0000269|PubMed:28365998}.
CC   -!- SIMILARITY: Belongs to the NmrA-type oxidoreductase family. Isoflavone
CC       reductase subfamily. {ECO:0000305}.
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DR   EMBL; KY764298; ARF05983.1; -; Genomic_DNA.
DR   SMR; A0A1W5T323; -.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0044281; P:small molecule metabolic process; IEA:UniProt.
DR   CDD; cd05259; PCBER_SDR_a; 1.
DR   InterPro; IPR016040; NAD(P)-bd_dom.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR045312; PCBER-like.
DR   Pfam; PF13460; NAD_binding_10; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   2: Evidence at transcript level;
KW   NADP; Oxidoreductase.
FT   CHAIN           1..314
FT                   /note="Oxidoreductase poxI"
FT                   /id="PRO_0000453771"
SQ   SEQUENCE   314 AA;  33846 MW;  AEB6D652E7952626 CRC64;
     MSTVYYPSVI LKKSPLPLKL TPARASGNFG TPITAALQRA SFNITIITRT ESSSTFPAGL
     PIIRTSYTLE NLTTALAGQD AAICVVGPGG IGAQVLMIEA AEAAGVKRFI VDDFGWGPGF
     RNLPEFRAIH AHRRAGWELA KAKAQANPNF TFTGITSGNP IDWAMKRFPL MGFDIARCSA
     IIYDSGTEKF TATTLAGIGQ SVVGVLQHPD ETANRFVKVL SIITNQNELL EAFQRVTGRQ
     WPVQRASAQT LIESGQQKFQ AGMGGWVLEL VVAQMYDEGE ARCVMAPSWE ASDSPLLGVK
     KESADEVVAK VLQL