POXJ_PENOX
ID POXJ_PENOX Reviewed; 345 AA.
AC A0A1W5T363;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2017, sequence version 1.
DT 03-AUG-2022, entry version 13.
DE RecName: Full=WD40 repeat protein poxJ {ECO:0000303|PubMed:28365998};
DE AltName: Full=Oxaleimides biosynthesis cluster protein J {ECO:0000303|PubMed:28365998};
GN Name=poxJ {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: WD40 repeat protein; 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 -!- 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 WD repeat rae1 family. {ECO:0000305}.
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DR EMBL; KY764299; ARF05984.1; -; Genomic_DNA.
DR SMR; A0A1W5T363; -.
DR GO; GO:0006406; P:mRNA export from nucleus; IEA:InterPro.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR037631; Gle2/RAE1.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR10971:SF11; PTHR10971:SF11; 1.
DR Pfam; PF00400; WD40; 3.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 2.
DR PROSITE; PS50294; WD_REPEATS_REGION; 2.
PE 2: Evidence at transcript level;
KW Repeat; WD repeat.
FT CHAIN 1..345
FT /note="WD40 repeat protein poxJ"
FT /id="PRO_0000453773"
FT REPEAT 15..49
FT /note="WD 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 59..100
FT /note="WD 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 101..146
FT /note="WD 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 250..284
FT /note="WD 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
SQ SEQUENCE 345 AA; 37841 MW; 6EFCE162864BCBD6 CRC64;
MVDNQGPLAK DVSLANPPSD SISELSWSPV ANHLAMSSWD QTVRIYDVSQ SGNGEGQALF
NFPAPVLSCT FSPDGAKVLG GATDGSARLM DLVAGKEAQQ VAAHDAPVRC VRFFGNPGVR
DPIAVTGSWD QTVKYWDLRQ DRPLATLQCQ ERVYAMDLCQ NLLVVATAGR LVHVVQLSNA
DQIYKTVTSP LKHQTRTVTC IPDASGFAIG STEGRTGFHY VDESKSSLNF TFRCHREMAA
SKNTQNVYAV NDVSFHPKYY TFSTAGADGT FAFWDKDAHH RLKSFPSVGA PITSTGFNHD
GTIFAYAVSY DWSKGFRYNT PEHPTRVVCH PVDDVDCRPK NPVKR
