POXN_PENO1
ID POXN_PENO1 Reviewed; 176 AA.
AC S8B3I8;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2013, sequence version 1.
DT 29-SEP-2021, entry version 12.
DE RecName: Full=Oxaleimides biosynthesis cluster protein N {ECO:0000303|PubMed:28365998};
GN Name=poxN {ECO:0000303|PubMed:28365998}; ORFNames=PDE_04026;
OS Penicillium oxalicum (strain 114-2 / CGMCC 5302) (Penicillium decumbens).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=933388;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=114-2 / CGMCC 5302;
RX PubMed=23383313; DOI=10.1371/journal.pone.0055185;
RA Liu G., Zhang L., Wei X., Zou G., Qin Y., Ma L., Li J., Zheng H., Wang S.,
RA Wang C., Xun L., Zhao G.-P., Zhou Z., Qu Y.;
RT "Genomic and secretomic analyses reveal unique features of the
RT lignocellulolytic enzyme system of Penicillium decumbens.";
RL PLoS ONE 8:E55185-E55185(2013).
RN [2]
RP FUNCTION, INDUCTION, AND PATHWAY.
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 [3]
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; KB644411; EPS29077.1; -; Genomic_DNA.
DR EnsemblFungi; EPS29077; EPS29077; PDE_04026.
DR HOGENOM; CLU_1525690_0_0_1; -.
DR OrthoDB; 1508574at2759; -.
DR PhylomeDB; S8B3I8; -.
DR Proteomes; UP000019376; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
PE 2: Evidence at transcript level;
KW Membrane; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..176
FT /note="Oxaleimides biosynthesis cluster protein N"
FT /id="PRO_0000453780"
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
