POXQ_PENOX
ID POXQ_PENOX Reviewed; 443 AA.
AC A0A1W5T317;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2017, sequence version 1.
DT 03-AUG-2022, entry version 7.
DE RecName: Full=Diels-Alderase poxQ {ECO:0000303|PubMed:32039410};
DE EC=5.5.1.- {ECO:0000269|PubMed:32039410};
DE AltName: Full=Oxaleimides biosynthesis cluster protein Q {ECO:0000303|PubMed:28365998};
DE Flags: Precursor;
GN Name=poxQ {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: Diels-Alderase; 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 Diels-Alderase family. {ECO:0000305}.
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DR EMBL; KY764306; ARF05991.1; -; Genomic_DNA.
DR SMR; A0A1W5T317; -.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
PE 2: Evidence at transcript level;
KW Glycoprotein; Isomerase; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..443
FT /note="Diels-Alderase poxQ"
FT /id="PRO_5012190531"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 97
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 443 AA; 49096 MW; 29246080C847D0C5 CRC64;
MARIPLEFLS ITLPVLLLAY CLAIEYEVSL PTIAHTSPAS NPEEYLQSIY EQLNLDLPST
CTVNHLSAFD NTPTSLLNFS TSPVEHFDAP KLPSGLNATA GEQWAFDGTS SSGRSGLLLG
IYRDASYAFL GPGNFRLSLD LVWDNSTTWS TVDYLSSSTV HTCTDKVVGI WSHSADHYYV
FTVTADAKHA RIHFHTPDVV GAVDLYSTTP ARYPDGALFP SEVSVTQNAP MLHWVEPIPG
GLIDVDLKVK DTPFRWTGLG GHERWWSAKG WLDLMTHWEA VRLMAGPYVL SFWQPTSRVN
GVAYPSAFLT KYGEKVFSAV SGKVSEVEDY ILYRPVRMEK QARETGYEVD LVSPAQGRRW
VFGLEYRNQE FEFELGDAAG GRAYVGRAKG GEVHADDKPE EPSEGVFFIE HVDVKALTVP
RAYVVVSFEF GPPIHGADIW VAC
