PPZA_METRR
ID PPZA_METRR Reviewed; 2879 AA.
AC A0A166YZW0;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 06-JUL-2016, sequence version 1.
DT 03-AUG-2022, entry version 36.
DE RecName: Full=Peramine synthetase ppzA {ECO:0000303|PubMed:30452111};
DE EC=2.3.2.- {ECO:0000269|PubMed:30452111};
DE AltName: Full=Nonribosomal peptide synthetase ppzA {ECO:0000303|PubMed:30452111};
DE Short=NRPS ppzA {ECO:0000303|PubMed:30452111};
DE AltName: Full=Pyrrolopyrazine biosynthesis cluster protein A {ECO:0000303|PubMed:30452111};
GN Name=ppzA {ECO:0000303|PubMed:30452111};
GN Synonyms=perA {ECO:0000303|PubMed:30452111}; ORFNames=NOR_07095;
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, DOMAIN, CATALYTIC ACTIVITY, 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: Nonribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of pyrrolopyrazines, secondary
CC metabolites 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 -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30452111}.
CC -!- DOMAIN: NRP synthetases are composed of discrete domains (adenylation
CC (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation
CC (C) domains) which when grouped together are referred to as a single
CC module. Each module is responsible for the recognition (via the A
CC domain) and incorporation of a single amino acid into the growing
CC peptide product. Thus, an NRP synthetase is generally composed of one
CC or more modules and can terminate in a thioesterase domain (TE) that
CC releases the newly synthesized peptide from the enzyme. Occasionally,
CC methyltransferase domains (responsible for amino acid methylation) are
CC present within the NRP synthetase. PpzA has the following architecture:
CC A-T-C-A-Met-T-TE. {ECO:0000305|PubMed:30452111}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; AZHC01000030; OAA37396.1; -; Genomic_DNA.
DR SMR; A0A166YZW0; -.
DR STRING; 1081105.A0A166YZW0; -.
DR EnsemblFungi; OAA37396; OAA37396; NOR_07095.
DR OrthoDB; 4243at2759; -.
DR Proteomes; UP000243498; Unassembled WGS sequence.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0009058; P:biosynthetic process; IEA:UniProt.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR CDD; cd05235; SDR_e1; 1.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.30.300.30; -; 3.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 2.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR013120; Far_NAD-bd.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR010080; Thioester_reductase-like_dom.
DR Pfam; PF00501; AMP-binding; 2.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 2.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 2.
DR TIGRFAMs; TIGR01746; Thioester-redct; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE 1: Evidence at protein level;
KW Ligase; Methyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Repeat; Transferase.
FT CHAIN 1..2879
FT /note="Peramine synthetase ppzA"
FT /id="PRO_0000450255"
FT DOMAIN 882..958
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2370..2448
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 351..747
FT /note="Adenylation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30452111"
FT REGION 997..1410
FT /note="Condensation"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30452111"
FT REGION 1433..1827
FT /note="Adenylation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30452111"
FT REGION 1958..2050
FT /note="Methylation (Met) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30452111"
FT REGION 2500..2817
FT /note="Thiesterase (TE) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30452111"
FT COMPBIAS 13..52
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 919
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2407
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2879 AA; 319057 MW; D5BDFE435539D559 CRC64;
MTYDEGGHRN NEETPQDVNM SSNNEGMSTS SPTGSYGEII GQATVSVPQE DQEKLTPLNE
LSGLYAERES YQSPLCPSTT KMISETVRKS SADDGYTSFP IRSTLIDRPV LDKTLRCEFA
LFPPFCDIQR LSTLSNASWA LIAGHLTNST KVIVGIPAFG ESTSVHNIES GTALQPAPIP
LLIDWRPEQS VMDYLKHVQS RIADVTTLGG AGSQLLTSGY PVNYNAGHLQ TLIVVETNEI
SPGSINGTRE VQLRQYDYKK KYACAALVIE IRLQKTGIVA VASFDTRALG PSLVYNLLKR
LEYVMEQLFR VSSDHVLADI DMVTSEDLEQ IWQWNDPIPA PVERCMHEMV QEQCRLQPNT
LAVDAWDGRL TYRELDQLSN RLACHLVDRG VEPDMFVPLC FHKSMWMPVT AMGVLKAGGA
FVLLEPSFPE QRLRAIVEET EASIVLASST TMALSLRLLD NVIQVDSELF NCLTFSANRL
PQLQPSSSAM FGVFTSGSTG KPKGAVLTHA NYCSALTYQL DLLGFKKDSR VFDFASYAFD
VSVHNIFASL ASGACLCIPS EEKRLEDICK SISDMRATIV HLTPSVARLI QPEKVPLLQT
VIFTGEPLSV EDVEQWWGKT NIVNEYGPAE CSINTINSNP SSPEEATLIG KGVGVAVWIV
DPSNHDLLVP IGSVGELLIE GALVGRGYIN ETEKNAAAFI ENPKWLLHGR PGRPGRQGRL
YKTGDLVKYG ENGNLAFVGR KDTQVKIYGQ RVDLREVEHW IQSCGQGAGQ VVAEMIAPRA
DDHDPAPALV AFLRNEHTAL DGSLCPNSTE AILRPVPDEV EARLSKHLPN YMVPKVFIVL
SKFPMTATGK TDRMQLRKIG SSFSLEQLAE VRAKTWAGPK RQPLSDMERL LCDVWSKVLG
LERRSIGPES NFFHLGGDSI AAMKSVGEAR KSGIKVAVAD VFRHPSLQDL SRQSKYIEDN
SLDHIKPFEL LGEEFNRLAF LKDASHQYGI DPSAIYDAYP CTPLQEGLMS LTAKRPGDYI
EQMILELGED VKIDNLWAAW KHVACVTPIL RTRLVHHNDL GLMQLVIEED TSWTDATGLD
EYLDADRKRS MNLGEPLSRY GLVRDETGEP KWFVWSIHHA IYDGWSVQLI LDAAYRAYSG
QEVEQGPQFQ EFIKYVQQQR HQNQKRVVEY WQKTLEGFEG AQFPPVVPSV QQPVANTAVR
HCIPNPPNGR VGVTMSMLIR AAWALVVGRM ANSDDVVYGS TLYGRNASVA GLDELAAPTI
ATVPLRIRLS SKKTVSEYLE AIQREATTMI PFEQTGLQEI AQMSDSCRMA CKFQTLLVIQ
PEEHSQGKGP LGTWQVRSQE QWFSTYPLTL ELWLGTDHIT ASAMFDSRII ESWVVRKMLQ
RLEGVMYQLN HATSSQLLGD ITILTTEDLE QIWEWNKTIP TPVNRCVHEI IHDKVQHRPN
APAICAWDGE ITYSELNRLA DKLSGRLTEL GVGPHLLVPL CFEKSLWTAV AILGVIKSGG
GFVLLDASLP EQRLRSIMKQ IKGDLVITCP SQQALCSRLG AETITLSWGF FSTLKDYEAG
LQIQSYSPSS ILYAVFTSGS TGIPKGVLIT HANMASALYY QSEVMGLSED SRLYDFASYS
FDVAISNMFT VLAAGGCLCV PSEEHRKNNL EGSIISLRAN ALDLTPSIAQ LLSPARLPNV
RSLTLGGEPV LATAVEQWFG KLQIRNAYGP SECTPTCIVN HNPSSPEQAT EIGNGVGIVT
WVVDPSNHEV LLPPGCTGEL LLEGPLVGPG YLDDGEKTAA AFVHDPVWLT KGTHNRSGRH
GLLYKTGDLA KYHENGTLSF VRRKDTTQIK LRGQRVELGE VEHILRSHSC VIDAVAASQC
DDKLGAWIAG FVTIRADGQK EHQGDEEYEQ QQIQSWEDQF DGETYTSIEE IPREAIGRDF
IGWTSMYDGS DLDKGEMNEW LNDTINTILD GGPAGHVLEI GCGSGMMLFN LANKGLQSYI
GIEPSKRAVD ATASIVKSIP HLKERVRIVK GTGEDLQQLG TPISPDLVVI NSVIQYFPSQ
KYLVKLIQDI LELRSVQTIF FGDVRSHALH KEFLALRALS IVGETASREE IGQVLSNLHR
AEPELLLDPE FFTSLPARLP GHIAHVEILP KKMEATNELS SFRYGAVVHV DLKHGQIRDI
DAKSWVSYTS QGLDCKSLLA LLKDWPHAAD TIAISDIPHS KTVFATKLID ELENGASEAR
HGRHWAEFIR QDAKQCCALS AIDLVKLAKE AGYRAEVSWA RQYSQRGGLD AVFHRFITDN
DARRVLFRFP IDHTNRPFHL LSSKPLRRRA EMNIQRELEA RLRCQLPSHM IPQTITILDR
MPISHNGKVD RQILADSVQR QWTGQERKRW PTTDTGKELQ RIWSHVLNIS PDSIGLDDGF
VHFGGNSLHA MKIVHMARQA GINLKVTDMF RHSETTIGRL LLDCCCDDTP GKSTSADPVH
WTYLMAAIDE KDKCLAAIQA GAKPRLVDGD IQADPDELFT VLLTGANGFI GTQILRQLLE
HGRVDRVICI VRGESTSVAR HRTIEAAQKA LWWTEFHQEM LEVWPGDLSA PRLGLDDAKW
RLLAEGKAVN IIIHNGASVN FVKGYAALEA VNVNSTVEMM SVVTRNPGMR FIYVSSARSQ
DPMEEEEEDM ARVLTENPNG YNQTKFVAEA LVRRAASRSS PRQHQFMVVS PGLVVGTPTE
GVANADDWLW RMAAACIRVG VYNVDDSDKW IPLCDVGTIA AVIIHAALGH PSSSTTVTQV
RGGLTMGEFW ETLATAGYPL TGTRVAECTA AIREDILANR EKHPLGVLED MLQDLDDTTN
VQWAASWRKN GLCSPARLKA ALCKSAEFLS GVSFLPLPNF VRERLVQETS MSAFTRSGF
