ID   PPZG_METRR              Reviewed;         251 AA.
AC   A0A166YZR3;
DT   17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT   06-JUL-2016, sequence version 1.
DT   03-AUG-2022, entry version 20.
DE   RecName: Full=Cytochrome P450 monooxygenase ppzG {ECO:0000303|PubMed:30452111};
DE            EC=1.-.-.- {ECO:0000305|PubMed:30452111};
DE   AltName: Full=Pyrrolopyrazine biosynthesis cluster protein G {ECO:0000303|PubMed:30452111};
GN   Name=ppzG {ECO:0000303|PubMed:30452111};
GN   ORFNames=NOR_07092 {ECO:0000312|EMBL:OAA37393.1};
OS   Metarhizium rileyi (strain RCEF 4871) (Nomuraea rileyi).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Clavicipitaceae; Metarhizium.
OX   NCBI_TaxID=1081105;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=RCEF 4871;
RX   PubMed=27071652; DOI=10.1093/gbe/evw082;
RA   Shang Y., Xiao G., Zheng P., Cen K., Zhan S., Wang C.;
RT   "Divergent and convergent evolution of fungal pathogenicity.";
RL   Genome Biol. Evol. 8:1374-1387(2016).
RN   [2]
RP   FUNCTION, AND PATHWAY.
RX   PubMed=30452111; DOI=10.1111/1462-2920.14483;
RA   Berry D., Mace W., Rehner S.A., Grage K., Dijkwel P.P., Young C.A.,
RA   Scott B.;
RT   "Orthologous peramine and pyrrolopyrazine-producing biosynthetic gene
RT   clusters in Metarhizium rileyi, Metarhizium majus and Cladonia grayi.";
RL   Environ. Microbiol. 21:928-939(2019).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of pyrrolopyrazines, secondary metabolites
CC       showing insecticidal activity (PubMed:30452111). The single
CC       multifunctional NRPS ppzA is responsible for the biosynthesis of
CC       peramine (PubMed:30452111). The condensation domain of ppzA is proposed
CC       to catalyze formation of a peptide bond between 1-pyrroline-5-
CC       carboxylate and arginine (By similarity). The methylation domain of
CC       ppzA would catalyze the N-methylation of the alpha-amino group of
CC       arginine (By similarity). The reductase domain is proposed to be
CC       responsible for reduction of the thioester and the cyclization to form
CC       an iminium ion resulting in release from the peptide synthetase (By
CC       similarity). Deprotonation of this intermediate and oxidation of the
CC       pyrroline ring would give rise to peramine (By similarity). This final
CC       oxidation to give the pyrrole functionality may be spontaneous (By
CC       similarity). In Epichloe species that produce only peramine, the
CC       peramine synthetase gene is not localized in a gene cluster, in
CC       contrast to Metarhizium rileyi that contains additionnal
CC       pyrrolopyrazine biosynthesis genes (Probable). The 2-oxoglutarate-
CC       Fe(II) type oxidoreductases ppzC and ppzD could be candidates for
CC       conversion of proline into an oxidized derivative to be used by the
CC       ppzA A1-domain as substrate (Probable). The other ppz genes encode
CC       proteins predicted to derivatize peramine into more complex
CC       pyrrolopyrazine metabolites (Probable). {ECO:0000250|UniProtKB:Q4H424,
CC       ECO:0000269|PubMed:30452111, ECO:0000305|PubMed:30452111}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:30452111}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; AZHC01000030; OAA37393.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A166YZR3; -.
DR   SMR; A0A166YZR3; -.
DR   STRING; 1081105.A0A166YZR3; -.
DR   EnsemblFungi; OAA37393; OAA37393; NOR_07092.
DR   OrthoDB; 1575971at2759; -.
DR   Proteomes; UP000243498; Unassembled WGS sequence.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   SUPFAM; SSF48264; SSF48264; 1.
PE   3: Inferred from homology;
KW   Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Reference proteome.
FT   CHAIN           1..251
FT                   /note="Cytochrome P450 monooxygenase ppzG"
FT                   /id="PRO_0000450264"
FT   BINDING         250
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:P04798"
SQ   SEQUENCE   251 AA;  27201 MW;  7149BB94A8DABBB2 CRC64;
     MNDFVFSDIP DNVKPMASVE FDDPLTIATG DVLNWTLWLT RNFPALSSII MRLPSSLVSM
     VTSSFEGANQ MVQVKTSTHN LYSLSLPTHA RKQIISQLVE HEKNHIGPKS KDCVMQRLLN
     AHRDSESKIS IPTPDATLRS EAVGFTLAGT ADPPNILALG TFMAARDSEM QKGLYKELKA
     IWPDLRSPAP SYNLLHQLPL LRGIIKESIR FTHGVATGPA RLVGAGGARI GGYNVPAKAS
     SFSAAATSDC S