POXP_PENOX
ID POXP_PENOX Reviewed; 378 AA.
AC A0A1W5T1Y4;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2017, sequence version 1.
DT 03-AUG-2022, entry version 11.
DE RecName: Full=Trans-enoyl reductase poxP {ECO:0000303|PubMed:28365998};
DE EC=1.-.-.- {ECO:0000305|PubMed:28365998};
DE AltName: Full=Oxaleimides biosynthesis cluster protein P {ECO:0000303|PubMed:28365998};
GN Name=poxP {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: Trans-enoyl reductase; part of the gene cluster that mediates
CC the biosynthesis of oxaleimides, cytotoxic compounds containing an
CC unusual disubstituted succinimide moiety (PubMed:28365998). The first
CC step of the pathway is provided by the HR-PKS poxF that serves in a new
CC mode of collaborative biosynthesis with the PKS-NRPS poxE, by providing
CC the 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 -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9Y7D0}.
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 zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; KY764305; ARF05990.1; -; Genomic_DNA.
DR SMR; A0A1W5T1Y4; -.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 2: Evidence at transcript level;
KW NADP; Nucleotide-binding; Oxidoreductase.
FT CHAIN 1..378
FT /note="Trans-enoyl reductase poxP"
FT /id="PRO_0000453755"
FT BINDING 62..65
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 151..158
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 187..190
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 210..213
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 228
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 275..276
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 295..299
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 364..365
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 378 AA; 40719 MW; 37032AFAA8B9810F CRC64;
MPVQPCSLPA GFLPAAVSLP SQQTVIAEDE TGKATIYHDA PLPIPEPHMV LVKTIAVSIN
PCDWKMPSRF PAPGARIGCD FAGIVLSIGP EAARIRRDLR IGDRVCGGIH GSNPIDLPSG
SFSQYVAAHA DLLLKLPNKL SFAQGAVLGG SVFATLWIAL YESLGLEGTP DMPLQDDPPP
VLVYGGSTST GTAALQILRL SGYRPIATCS PHNNDLVRAA GAEKVFDYRS ETCAADIKSY
TNGRLRHVLD IITDLQSQLI CYDTFSRVGG KYTCLEQPAE ELHLRRTVRK EMIVGLAASG
KEIALADGYE RTANPQLRAR SGEFFQTIQR LVDEGKFVPH PTRTVEGGFE GILKCLDILK
SGGTSGEKLV VFVDRENP
