ID   PPZF_METRR              Reviewed;         340 AA.
AC   A0A166YZT6;
DT   17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT   06-JUL-2016, sequence version 1.
DT   25-MAY-2022, entry version 13.
DE   RecName: Full=Pyrrolopyrazine biosynthesis cluster protein F {ECO:0000303|PubMed:30452111};
GN   Name=ppzF {ECO:0000303|PubMed:30452111}; ORFNames=NOR_07093;
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: Part of the gene cluster that mediates the biosynthesis of
CC       pyrrolopyrazines, secondary metabolites showing insecticidal activity
CC       (PubMed:30452111). The single multifunctional NRPS ppzA is responsible
CC       for the biosynthesis of peramine (PubMed:30452111). The condensation
CC       domain of ppzA is proposed to catalyze formation of a peptide bond
CC       between 1-pyrroline-5-carboxylate and arginine (By similarity). The
CC       methylation domain of ppzA would catalyze the N-methylation of the
CC       alpha-amino group of arginine (By similarity). The reductase domain is
CC       proposed to be responsible for reduction of the thioester and the
CC       cyclization to form an iminium ion resulting in release from the
CC       peptide synthetase (By similarity). Deprotonation of this intermediate
CC       and oxidation of the pyrroline ring would give rise to peramine (By
CC       similarity). This final oxidation to give the pyrrole functionality may
CC       be spontaneous (By similarity). In Epichloe species that produce only
CC       peramine, the peramine synthetase gene is not localized in a gene
CC       cluster, in 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   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:30452111}.
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DR   EMBL; AZHC01000030; OAA37394.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A166YZT6; -.
DR   EnsemblFungi; OAA37394; OAA37394; NOR_07093.
DR   OrthoDB; 996820at2759; -.
DR   Proteomes; UP000243498; Unassembled WGS sequence.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   SUPFAM; SSF52540; SSF52540; 1.
PE   3: Inferred from homology;
KW   Reference proteome.
FT   CHAIN           1..340
FT                   /note="Pyrrolopyrazine biosynthesis cluster protein F"
FT                   /id="PRO_0000450265"
SQ   SEQUENCE   340 AA;  38520 MW;  1AC6BF215560D68A CRC64;
     MSAHPGKPGR YYLISYPRTA SNLLLKILAL DSQPNFSSGE VDGGYFFMPA DDILIEPRIR
     ARSIGDWTAD ERAQVKESFQ ACFEAQQQWL EATESQGRSV FVKEHTVFFA DPTARSDLQF
     GPSPTREPAW TVEYAGGSTH SKLNITVLPD EFLLTWLPTF LIRHPALAFP SLYRTVIKRE
     GKESAAADNF ASLLTTVEWS RSLYDFYVQN RESLPCSPDQ SLEWPMILDA DDIIAHPATV
     ALYCNKIGMD PRKLCFHWDQ FKSEELSQIE PNQLAMRMSL YQSTGIDTSK SSRGINVDDE
     ASKWRSEFGI AVGDHIEKLV RGAMADYEYL RARRLRADRG