ID   POXN_PENOX              Reviewed;         176 AA.
AC   A0A1W5T1Y3;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2017, sequence version 1.
DT   29-SEP-2021, entry version 6.
DE   RecName: Full=Oxaleimides biosynthesis cluster protein N {ECO:0000303|PubMed:28365998};
GN   Name=poxN {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: Part of the gene cluster that mediates the biosynthesis of
CC       oxaleimides, cytotoxic compounds containing an unusual disubstituted
CC       succinimide moiety (PubMed:28365998). The first step of the pathway is
CC       provided by the HR-PKS poxF that serves in a new mode of collaborative
CC       biosynthesis with the PKS-NRPS poxE, by providing the olefin containing
CC       amino acid substrate via the synthesis of an ACP-bound dec-4-enoate
CC       (PubMed:28365998). The cytochrome P450 monooxygenase poxM-catalyzed
CC       oxidation at the alpha-position creates the enzyme-bound 2-hydroxydec-
CC       4-enoyl-ACP thioester, which may be prone to spontaneous hydrolysis to
CC       yield 2-hydroxydec-4-enoic acid due to increased electrophilicity of
CC       the carbonyl (PubMed:28365998). 2-hydroxydec-4-enoic acid can then be
CC       further oxidized by poxM to yield the alpha-ketoacid 2-oxodec-4-
CC       enoicacid, which is reductively aminated by the aminotransferase poxL
CC       to yield (S,E)-2-aminodec-4-enoic acid (PubMed:28365998). The Hybrid
CC       PKS-NRPS synthetase poxE then performs condensation between the
CC       octaketide product of its PKS modules and the amino group of (S,E)-2-
CC       aminodec-4-enoic acid which is activated and incorporated by the
CC       adenylation domain (PubMed:28365998). The resulting aminoacyl product
CC       can be cyclized by the Diels-Alderase PoxQ and reductively released by
CC       the reductive (R) domain of poxE to yield an aldehyde intermediate
CC       (PubMed:28365998) (Probable). The released aldehyde is then substrate
CC       for a Knoevenagel condensation by the hydrolyase poxO followed by an
CC       oxidation at the 5-position of the pyrrolidone ring (PubMed:28365998).
CC       The presence of the olefin from the amino acid building block allows
CC       for migration of the substituted allyl group to occur
CC       (PubMed:28365998). This allylic transposition reaction takes place in a
CC       conjugate addition, semipinacol-like fashion to yield a succinimide
CC       intermediate (PubMed:28365998). Iterative two-electron oxidations of
CC       the C7 methyl of the succinimide intermediate to the carboxylic acid
CC       can be catalyzed by one of two remaining cytochrome P450
CC       monooxygenasess poxC or poxD to yield oxaleimide A (PubMed:28365998).
CC       Subsequent oxidation yields the maleimide scaffold oxaleimide I
CC       (PubMed:28365998). Both oxaleimide A and oxaleimide I can undergo
CC       oxidative modifications in the decalin ring to yield the series of
CC       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   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- INDUCTION: Expression is positively regulated by the oxaleimides
CC       biosynthesis cluster-specific transcription factor poxB.
CC       {ECO:0000269|PubMed:28365998}.
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DR   EMBL; KY764303; ARF05988.1; -; Genomic_DNA.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
PE   2: Evidence at transcript level;
KW   Membrane; Transmembrane; Transmembrane helix.
FT   CHAIN           1..176
FT                   /note="Oxaleimides biosynthesis cluster protein N"
FT                   /id="PRO_0000453779"
FT   TRANSMEM        5..25
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        71..91
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        104..124
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        155..175
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   176 AA;  19634 MW;  DDF13E2341C57586 CRC64;
     MALDLLVVSA GSLALKVLRV TPLITTTILL VNRLAQYFAL STFLPPHTSP KKIDHVGAAF
     QHWLQTVVPR VWTGVISIVL FTRVALILNL FVRPDDLAGS NARFLYGVGL FLSFAHLSVA
     PKMLKFEKRM MSPETVPHVA MELLAGWMKV NNIRFWIVDV PFWVVGVWAT LEGLKA