AMT1_ALTAL
ID AMT1_ALTAL Reviewed; 4363 AA.
AC C9K7B5; C9K7D5; C9K7H7; Q9UVN5;
DT 18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 1.
DT 23-FEB-2022, entry version 49.
DE RecName: Full=AM-toxin synthetase AMT1 {ECO:0000303|PubMed:10875335};
DE EC=6.3.2.- {ECO:0000305|PubMed:10875335};
DE AltName: Full=Cyclic peptide synthetase AMT {ECO:0000303|PubMed:10875335};
DE AltName: Full=Nonribosomal peptide synthetase AMT1 {ECO:0000303|PubMed:17990954};
DE Short=NRPS AMT1 {ECO:0000305};
GN Name=AMT1 {ECO:0000303|PubMed:15066029};
GN Synonyms=AMT {ECO:0000303|PubMed:10875335};
OS Alternaria alternata (Alternaria rot fungus) (Torula alternata).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Pleosporomycetidae; Pleosporales; Pleosporineae; Pleosporaceae; Alternaria;
OC Alternaria sect. Alternaria; Alternaria alternata complex.
OX NCBI_TaxID=5599;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
RC STRAIN=M-71;
RX PubMed=10875335; DOI=10.1094/mpmi.2000.13.7.742;
RA Johnson R.D., Johnson L., Itoh Y., Kodama M., Otani H., Kohmoto K.;
RT "Cloning and characterization of a cyclic peptide synthetase gene from
RT Alternaria alternata apple pathotype whose product is involved in AM-toxin
RT synthesis and pathogenicity.";
RL Mol. Plant Microbe Interact. 13:742-753(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=NBRC 8984;
RX PubMed=15066029; DOI=10.1111/j.1365-2958.2004.04004.x;
RA Ito K., Tanaka T., Hatta R., Yamamoto M., Akimitsu K., Tsuge T.;
RT "Dissection of the host range of the fungal plant pathogen Alternaria
RT alternata by modification of secondary metabolism.";
RL Mol. Microbiol. 52:399-411(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND INDUCTION.
RC STRAIN=NBRC 8984;
RX PubMed=17990954; DOI=10.1094/mpmi-20-12-1463;
RA Harimoto Y., Hatta R., Kodama M., Yamamoto M., Otani H., Tsuge T.;
RT "Expression profiles of genes encoded by the supernumerary chromosome
RT controlling AM-toxin biosynthesis and pathogenicity in the apple pathotype
RT of Alternaria alternata.";
RL Mol. Plant Microbe Interact. 20:1463-1476(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-4175.
RC STRAIN=NBRC 8984;
RA Harimoto Y., Kodama M., Yamamoto M., Otani H., Tsuge T.;
RT "A Zn(II)2Cys6 transcription regulator encoded by the AMT gene cluster
RT negatively controls AM-toxin production in the apple pathotype of
RT Alternaria alternata.";
RL Submitted (OCT-2009) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION.
RX PubMed=11570518; DOI=10.1007/s002940100233;
RA Johnson L.J., Johnson R.D., Akamatsu H., Salamiah A., Otani H., Kohmoto K.,
RA Kodama M.;
RT "Spontaneous loss of a conditionally dispensable chromosome from the
RT Alternaria alternata apple pathotype leads to loss of toxin production and
RT pathogenicity.";
RL Curr. Genet. 40:65-72(2001).
RN [6]
RP REVIEW ON HOST-SELECTIVE TOXINS.
RX PubMed=22846083; DOI=10.1111/j.1574-6976.2012.00350.x;
RA Tsuge T., Harimoto Y., Akimitsu K., Ohtani K., Kodama M., Akagi Y.,
RA Egusa M., Yamamoto M., Otani H.;
RT "Host-selective toxins produced by the plant pathogenic fungus Alternaria
RT alternata.";
RL FEMS Microbiol. Rev. 37:44-66(2013).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene clusters
CC that mediate the biosynthesis of AM-toxins, host-selective toxins
CC (HSTs) causing Alternaria blotch on apple, a worldwide distributed
CC disease (PubMed:10875335, PubMed:17990954, PubMed:11570518). AM-toxins
CC are cyclic depsipeptides containing the 3 residues 2-hydroxy-isovaleric
CC acid (2-HIV), dehydroalanine, L-alanine which are common for all 3 AM-
CC toxins I to III. The fourth precursor is L-alpha-amino-methoxyphenyl-
CC valeric acid (L-Amv) for AM-toxin I, L-alpha-amino-phenyl-valeric acid
CC (L-Apv) for AM-toxin II, and L-alpha-amino-hydroxyphenyl-valeric acid
CC (L-Ahv) for AM-toxin III (Probable). AM-toxins have two target sites
CC for affecting susceptible apple cells; they cause invagination of the
CC plasma membrane and electrolyte loss, and chloroplast disorganization
CC (PubMed:22846083). The non-ribosomal peptide synthetase AMT1 contains 4
CC catalytic modules and is responsible for activation of each residue in
CC AM-toxin (PubMed:10875335). The aldo-keto reductase AMT2 catalyzes the
CC conversion of 2-keto-isovaleric acid (2-KIV) to 2-hydroxy-isovaleric
CC acid (2-HIV), one of the precursor residues incorporated by AMT1 during
CC AM-toxin biosynthesis, by reduction of its ketone to an alcohol
CC (PubMed:15066029). The cytochrome P450 monooxygenase AMT3 and the
CC thioesterase AMT4 are also important for AM-toxin production, but their
CC exact function within the AM-toxin biosynthesis are not known yet
CC (PubMed:17990954). Up to 21 proteins (including AMT1 to AMT4) are
CC predicted to be involved in AM-toxin biosynthesis since their
CC expression ishighly up-regulated in AM-toxin-producing cultures
CC (PubMed:17990954). {ECO:0000269|PubMed:10875335,
CC ECO:0000269|PubMed:11570518, ECO:0000269|PubMed:15066029,
CC ECO:0000269|PubMed:17990954, ECO:0000303|PubMed:22846083,
CC ECO:0000305|PubMed:10875335}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:10875335}.
CC -!- INDUCTION: Expression is up-regulated more than 10 fold in toxin
CC producing cultures. {ECO:0000269|PubMed:17990954}.
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 epimerase (E) domains (responsible for L- to D-amino acid conversion)
CC are present within the NRP synthetase (By similarity). AMT1 has the
CC following architecture: A-T-C-A-T-C-A-T-C-T-C (Probable).
CC {ECO:0000250|UniProtKB:Q4WAZ9, ECO:0000305|PubMed:10875335}.
CC -!- DISRUPTION PHENOTYPE: Reduces AM-toxin production to undetectable
CC levels. {ECO:0000269|PubMed:10875335}.
CC -!- MISCELLANEOUS: Gene clusters encoding host-selective toxins (HSTs) are
CC localized on conditionally dispensable chromosomes (CDCs), also called
CC supernumerary chromosomes, where they are present in multiple copies
CC (PubMed:17990954, PubMed:11570518). The CDCs are not essential for
CC saprophytic growth but controls host-selective pathogenicity
CC (PubMed:17990954, PubMed:11570518). {ECO:0000269|PubMed:11570518,
CC ECO:0000269|PubMed:17990954}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF01762.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF184074; AAF01762.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AB525198; BAI44739.1; -; Genomic_DNA.
DR EMBL; AB525200; BAI44801.1; -; Genomic_DNA.
DR EMBL; AB525199; BAI44759.1; -; Genomic_DNA.
DR SMR; C9K7B5; -.
DR PHI-base; PHI:160; -.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR Gene3D; 1.10.1200.10; -; 4.
DR Gene3D; 3.30.300.30; -; 4.
DR Gene3D; 3.30.559.10; -; 4.
DR Gene3D; 3.40.50.12780; -; 3.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
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; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR Pfam; PF00501; AMP-binding; 3.
DR Pfam; PF13193; AMP-binding_C; 1.
DR Pfam; PF00668; Condensation; 4.
DR Pfam; PF00550; PP-binding; 4.
DR SMART; SM00823; PKS_PP; 4.
DR SUPFAM; SSF47336; SSF47336; 4.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 3.
DR PROSITE; PS00455; AMP_BINDING; 3.
DR PROSITE; PS50075; CARRIER; 4.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 4.
PE 2: Evidence at transcript level;
KW Isomerase; Ligase; Phosphopantetheine; Phosphoprotein; Repeat; Virulence.
FT CHAIN 1..4363
FT /note="AM-toxin synthetase AMT1"
FT /id="PRO_0000444812"
FT DOMAIN 810..887
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1884..1961
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2977..3053
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3730..3806
FT /note="Carrier 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 278..670
FT /note="Adenylation 1"
FT /evidence="ECO:0000255"
FT REGION 926..1340
FT /note="Condensation 1"
FT /evidence="ECO:0000255"
FT REGION 1368..1765
FT /note="Adenylation 2"
FT /evidence="ECO:0000255"
FT REGION 1999..2410
FT /note="Condensation 2"
FT /evidence="ECO:0000255"
FT REGION 2448..2853
FT /note="Adenylation 3"
FT /evidence="ECO:0000255"
FT REGION 3098..3503
FT /note="Condensation 3"
FT /evidence="ECO:0000255"
FT REGION 3850..4204
FT /note="Condensation 4"
FT /evidence="ECO:0000255"
FT MOD_RES 847
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1922
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3014
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3767
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT CONFLICT 2986
FT /note="L -> I (in Ref. 4; BAI44801)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 4363 AA; 479692 MW; 2B1DE2FFE532F0C0 CRC64;
MELNDDPTGK IISGVNDISL PSLSAKQVAQ SLSEQLSTSA LPAIQSFSFP PLPNGLSETF
HDKKMDLSYA FPRKLMSALE VSSMFCAAWA IAVDRYTTND DVVFGAFLQD IPNPGLVPLR
LKTRSETDVG GLLHYVISEI TQSCNYPYLG KEKSSELSTE RQDSHEVGAM LVFGKSGAGE
SNVLYEKPIT CALTITCTLA GDQLHIGASY DSRVIEAPML TRVLRQFGYL ATQLADANPT
RRLTDIAQEL NRQDLEDIWK TNMEITTESG ALIQEIFAGQ AKQRPHAIAV EAWDGVLSYG
QLESLSTGLA HALLQLGIKD HSLIPFCLKN SKWAVVAMLG ILKANCTFVP IDSSSPWDRR
NRILELTHAE VIITSSFMSD DNLWNTSVLC LTEETVSGFP VLSNLPGRIS GPGSAAYVLF
TSGSTGDPKG VVVAHSAICN SLHAIGSKIG LDETSRTLQF TSLAFDISIF EILGTLIFGG
TICVPSEDDR LTRLPEYIVS AQVNTASLTP SVARLYDAAM VPCLNTLILG GEAMTRADIK
NWCRLPNLFN GFGPTETAIG CAMHRVHAEQ KQHSLIGRLA GIPVWVVDPS DHEVLVPFGA
VGELVVEGTT LALGYLDDDI KTQAAFIQDP PWLLRGCGVE LPGRRGRIYK TGDLVQYNEE
GSLLYVGRKD SDTQVKIRGN RVDLGEIESH LHECLPSRSE VVVDVVLPSD APTSSDHILA
VFLRYEGVNT LQDSTERTIP TKLIQVPEGI QKHLYSKLPA YMVPTVYFSV AVIPKMISGK
TDRKRLRGMA SLFSMQELAA NSSHQTVKRA PDSVIARQLQ GIWAQVLHVD PLAIGMDDSF
FALGGDSIAA IRLVREARQT FSIGLTVADI FSFPSLGALA AIAKVIPLID PGPSPAFTSL
RGVSSITDLL KDVAESCGLK QPSLIEDVYA CTPLQEGLLA LSSKHSGTYT VQRVLELAPD
VDIARFQAAW ETTARCTPIM RTRIVQHVEL GLLQAVVDED IEWKTLPSEQ LDSFLLADQK
TSMALGQPLM RYALTQGPYS GTHGSRHLVW TVHHALYDGW SLPLLLERVR QAYYGEQPQL
SEFAPFIRWC EQDVDEDSAA RHWQTYLEEA DESALFPPLP PSITEPIEDQ QAENRWALPE
HGTTAVTRSI VLRAAWAIVA SRYTSSNDVL FGTTVSGRGA PVPGIEEMVG PTVATVPTRC
KIDDNKSASS FLLEVQQAAV EAIPFEQTGL KRISEIDTRL RRVREIQTFL VVQPAEYGEA
AFEGLGKWVN GPGYYRLDVS ALTLECVLTE SGVRCVAYFD SHVIQAATVT RALAQFAHVS
QQLCTASPNT TLGQIDVLTS SDLRDIWNWN GPLLQLAEEP LPHVDIGKQA RTRPGAIAVH
SWDAQLTYQE LDKYSSLLAK QLLDADVKGG DIVPLYFEPS AWVVVAMLAV LKSGAAFTPI
DTSQPEQRRN RIVSQLQPSI GLVSARHATT VFGPGWATLE VSRRALSSMP EGPLGQVDAS
SIAWVIFTSG STGLPKGAML QHSAVHTSHR ALGATFGLCA NTRMLQFSSF AFDACVLEIV
ATLMHGGCVC IPSELQQRSL SELPSVCAAM EVNTMVLTPT VARLFGPSDF PDLTTLVLTG
EPLVQSDVTK WSSIAYVANG YGPAECSNIC TVHRIAPDDT DPNRIGSLRG VPNWVVHSRN
HHQLTPIGGV GELLIEGATV GHGYLNDAEK TAAAFVTDPA WLTEISHALP CFERHGRLYK
TGDIVKLHED GSLSYLGRKD TQIKIHGQRI ELGEIEHHVL HCTKAVEVTV DAVYVPGEEK
NKSLVAFVRP SNGTSTPQFY DNPDAIINEL ANSLPAYMIP TMYIQVPSIP RTASGKTDRK
QLREMGTAMA SSHAARHWKH QNRPPVTDME KHVQKLWARV LTLENAGEIS LDDSFIRLGG
DSIAAMKLVS LAAKAGLGLT VAQIFRHTKL EDQARHVTLL TQGGPAPIAQ FSLLPDSPDV
KALQADIARA YAIEASSIED VYPCTPLQEG LLSLSSKPSE YNTYTLQHVF ELPPTVDIQQ
LRSAWEETIR TTDILRTRIV LHPRYGLVQV VVKEEIQWHE PANADVYIET DKQVQMVLGS
SLVRYAISPD TGSASRKFIW TIHHALADGW TLDLILRKVK LAYSTLHTVS PVSEFRSFVK
YITTRNTDEM VEYWKSTLGG YHSTTFPALP SSVRYAIEDS EVGQKHELPR NITLSAHPLS
TLLRAAWAIV QSNYSNTSDV VFGEVFSGRS ASVPFIEAIV GPTMATLPVR VKIDDSELAR
EMLDRLLTTT TQMIPHEQLG LQRISQINTD CQAACSFQTL LVIQPPASTH NGQEEPSLSF
SGSPDYRLAT YALGIECTPA SDGYSFSCRA RFDSRVLSAQ VAERMMAQLG HVVSQLVAVT
ASPSSSTLVS DIVLNTPQDL EKLWAWNEAV LELGEEQKHS MLLHQVFRKK ALAAPQATAI
SSWDGECSYA QLEKLSDALA AMLTDLGIGI GLDQQLVPLC FERSMWVVVA MMAVLKTGAG
IVPLDPAHPP SRHERILAKV GIGGCILVSP QYAQRQFGEG WTTMVVSEAS AAAVPSIHAF
DPPTVTHLAV CWILFTSGST GEPKGIYLEH GAICASYKLL GKTLGIDKET RMLHFSAYAF
DIATFEIIGT LMSGGCICIP SDAERLERLP QFCTTFAVNT AILTPSVARL YTPNDIPTLR
SLCLAGEAPN KQDISTWQHR IPFLFNCYGP AEAACLAATN RIGPNDADRS ATRIGRLRGV
PLWITAPGNC RKLAPIGAVG ELLIEGSTLA RGYLDPTQTD AAFIEDPEWL LQGPAGERSG
RRGRLYRTGD LARYDEDGGV VYEGRKDNQV KIRGQRTELG EIEYHLSQCF PTAAEVVVEV
ATSERDLASV TLVAFVKSRE TRDSSEKVPA GIFALPSKLE HEINRRLPLY MIPAVFVSVP
EIPKTATDKT DRQKLRELAS VYATRAVDAP HHQPQRLPST VMEETLRDLW LKVIPVRQTA
IGLDSNFFRL GGDSIAALKL VGQAQQAGIE LSSKDIFLNP KLVDLAACCT DRRCVKEGSR
MVAKHATISR FSLLPINASI SSIVDEVANA CGIPPRLVED VYPCTPMQEG LMSLSSRNPG
TYVSQIAIEL APDVLVDLFK LAWQQTVSTM PILRSRIIQH PKLGFLQAVL KEDVTWNNST
DLDEYLETDS STPMGFGSEL SRHALVWDNS GKHIRFVWTV HHSIYDHVTL RLILDDVYDN
YKGNERKDFQ PYTSFVRSVI SMKSSESEEF WRNACKDEGS SIFPQRSLSI RESCEDTTVE
QSYQLCTTAT GVTMANVLHA AWAVVSSWHV GNQSIVFGTV LSGRTAPVLG IENIAGPTIA
TAPFPVIIDP SETISNFLQR IQGQMAAVIP HAQLGLQRIS RLSSACELAC NFQTLFAVQE
GRAMVGNSLG KLLDVNTFSM RTYALTLDCF LDTEGFHVKA SFDSRVVDQW RMESILRQFG
AVAQQLATKA EGGELVSSIE TLNEQGWELL RRWNSHRTHK QWAVFPEDCE KPSPIGAIGE
LLIEGPDFPS KYLEDPGARK VRSPRWMDRN GHKTVLLTGI LVAFDQNGNS IHIGQKRTTI
SFKGQRIDVS QIERHITSFL AGTEAVVEAI AIPSAENSQS VLAVFLHRPE LADRGDNKSR
PAICWSKDYG DIEKNLSVVF PDMVPTLYID MEAMPRTSHG DIDRSQLQTL GSLFPAEKVA
ILRASRQKRP AVTAMQLAIR GLWASLLGAK EDTFHLDDDF FKSGGDSIGV IKLVGEARKR
NIALAAADIF QYPKLESLAV RATENTLSQA EELEEPFSLI TSYVDDADRI EDFLSSNILS
RIPYAREALQ DVLPCTSMQK QLFHAQGQIY RFVLDFGDAQ IDAHRLEHAV HGLIDRHAIL
RTLFVPYQTD LLQVVVSPGK LKGRFVAETL GDGDEIEAAV ERVVSADKAD TNITGCPMPQ
FIFLSKRSKT EGFQSKLIIA RFSHMQFDGY SVPFVIRDLA TLYAATTSNT NTLDADEERT
LIVASETLPP APQFSSYIYA HYSTSSLERR KYWMRLLRAS YMTPITVKCD TPERIYNHTR
YENRTVELEA WYRIASSGQS SPDDILTMAW ALTLSIASEE SDIVFGRTVA GRRALFIPHG
GADDIMGPCV NTIPVRVQLP STTEQEEVDK SMTLRDLLAE IHKQTKETLP FESTGLDEIV
EHYAPSIWKK KPRRWTSTVV WQDFAGMQAV QHTVHRRSGN HEPNGEEKYE KVGQEDGSVA
LGYMDPFAAS SNVAFADLTC RVTCEIPLFD PADVAVIGRL VDGSPCFALG FAPERVPEPT
IKRLADTLMA VVLCLAEHPE TSVKHLLRAQ RENWRSIREL PNV
