ID   ACTS4_ALTAL             Reviewed;        1507 AA.
AC   A0A125SUR3;
DT   18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT   13-APR-2016, sequence version 1.
DT   25-MAY-2022, entry version 28.
DE   RecName: Full=Nonribosomal peptide synthetase ACTTS4 {ECO:0000303|Ref.1};
DE            EC=6.3.2.- {ECO:0000305|Ref.1};
DE   AltName: Full=ACT-toxin biosynthesis protein S4 {ECO:0000303|Ref.1};
GN   Name=ACTTS4 {ECO:0000303|Ref.1};
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], AND FUNCTION.
RC   STRAIN=Tangerine pathotype;
RA   Katsumoto M., Ogawa M., Miyamoto Y., Ishimoto T., Masunaka A., Ohtani K.,
RA   Mochizuki S., Tsuge T., Yamamoto M., Gomi K., Ichimura K., Peever T.L.,
RA   Akimitsu K.;
RT   "A non-ribosomal peptide synthetase gene ACTTS4 required for biosynthesis
RT   of ACT-toxin in the tangerine pathotype of Alternaria alternata.";
RL   Submitted (FEB-2015) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION.
RX   PubMed=18944496; DOI=10.1094/phyto.2000.90.7.762;
RA   Masunaka A., Tanaka A., Tsuge T., Peever T.L., Timmer L.W., Yamamoto M.,
RA   Yamamoto H., Akimitsu K.;
RT   "Distribution and characterization of AKT homologs in the tangerine
RT   pathotype of Alternaria alternata.";
RL   Phytopathology 90:762-768(2000).
RN   [3]
RP   FUNCTION.
RC   STRAIN=SH20;
RX   PubMed=18986255; DOI=10.1094/mpmi-21-12-1591;
RA   Miyamoto Y., Masunaka A., Tsuge T., Yamamoto M., Ohtani K., Fukumoto T.,
RA   Gomi K., Peever T.L., Akimitsu K.;
RT   "Functional analysis of a multicopy host-selective ACT-toxin biosynthesis
RT   gene in the tangerine pathotype of Alternaria alternata using RNA
RT   silencing.";
RL   Mol. Plant Microbe Interact. 21:1591-1599(2008).
RN   [4]
RP   FUNCTION.
RC   STRAIN=SH20;
RX   PubMed=19271978; DOI=10.1094/phyto-99-4-0369;
RA   Miyamoto M., Ishii Y., Honda A., Masunaka A., Tsuge T., Yamamoto M.,
RA   Ohtani K., Fukumoto T., Gomi K., Peever T.L., Akimitsu K.;
RT   "Function of genes encoding acyl-CoA synthetase and enoyl-CoA hydratase for
RT   host-selective act-toxin biosynthesis in the tangerine pathotype of
RT   Alternaria alternata.";
RL   Phytopathology 99:369-377(2009).
RN   [5]
RP   FUNCTION.
RC   STRAIN=SH20;
RX   PubMed=20055645; DOI=10.1094/phyto-100-2-0120;
RA   Ajiro N., Miyamoto Y., Masunaka A., Tsuge T., Yamamoto M., Ohtani K.,
RA   Fukumoto T., Gomi K., Peever T.L., Izumi Y., Tada Y., Akimitsu K.;
RT   "Role of the host-selective ACT-toxin synthesis gene ACTTS2 encoding an
RT   enoyl-reductase in pathogenicity of the tangerine pathotype of Alternaria
RT   alternata.";
RL   Phytopathology 100:120-126(2010).
RN   [6]
RP   FUNCTION.
RC   STRAIN=SH20;
RX   PubMed=20192828; DOI=10.1094/mpmi-23-4-0406;
RA   Miyamoto Y., Masunaka A., Tsuge T., Yamamoto M., Ohtani K., Fukumoto T.,
RA   Gomi K., Peever T.L., Tada Y., Ichimura K., Akimitsu K.;
RT   "ACTTS3 encoding a polyketide synthase is essential for the biosynthesis of
RT   ACT-toxin and pathogenicity in the tangerine pathotype of Alternaria
RT   alternata.";
RL   Mol. Plant Microbe Interact. 23:406-414(2010).
RN   [7]
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 the host-selective toxins (HSTs) ACT-
CC       toxins responsible for brown spot of tangerine disease by the tangerine
CC       pathotype which affects tangerines and mandarins (PubMed:19271978).
CC       ACT-toxins consist of three moieties, 9,10-epoxy-8-hydroxy-9-methyl-
CC       decatrienoic acid (EDA), valine and a polyketide (PubMed:22846083).
CC       ACT-toxin I is toxic to both citrus and pear; toxin II the 5''-deoxy
CC       derivative of ACT-toxin I, is highly toxic to pear and slightly toxic
CC       to citrus (PubMed:22846083). On cellular level, ACT-toxins affect
CC       plasma membrane of susceptible cells and cause a sudden increase in
CC       loss of K(+) after a few minutes of toxin treatment (PubMed:22846083).
CC       The acyl-CoA ligase ACTT1, the hydrolase ACTT2, the enoyl-CoA
CC       hydratases ACTT3 and ACTT6, and the acyl-CoA synthetase ACTT5 are all
CC       involved in the biosynthesis of the AK-, AF- and ACT-toxin common 9,10-
CC       epoxy-8-hydroxy-9-methyl-decatrienoic acid (EDA) structural moiety
CC       (PubMed:18944496, PubMed:18986255, PubMed:19271978). The exact role of
CC       each enzyme, and of additional enzymes identified within the AF-toxin
CC       clusters have still to be determined (PubMed:18944496, PubMed:18986255,
CC       PubMed:19271978). On the other hand, ACTTS1 to ACTTS4 are specific to
CC       the tangerine pathotype (PubMed:22846083). The function of ACTTS3 is to
CC       elongate the polyketide chain portion of ACT-toxin that is unique to
CC       this toxin (PubMed:20192828). The enoyl-reductase ACTTS2 might
CC       complement the missing enoyl-reductase (ER) domain in ACTTS3 in the
CC       synthesis of the polyketide portion of ACT-toxin (PubMed:20055645). The
CC       roles of the nonribosomal peptide synthetases-related proteins ACTTS1
CC       and ACTTS4 have also still not been elucidated (PubMed:22846083).
CC       {ECO:0000269|PubMed:18944496, ECO:0000269|PubMed:18986255,
CC       ECO:0000269|PubMed:19271978, ECO:0000269|PubMed:20055645,
CC       ECO:0000269|PubMed:20192828, ECO:0000303|PubMed:22846083}.
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|Ref.1}.
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 (By similarity). Each module is responsible for the recognition
CC       (via the A domain) and incorporation of a single amino acid into the
CC       growing peptide product. Thus, an NRP synthetase is generally composed
CC       of one or more modules and can terminate in a thioesterase domain (TE)
CC       that releases the newly synthesized peptide from the enzyme.
CC       Occasionally, methyltransferase domains (responsible for amino acid
CC       methylation) are present within the NRP synthetase (By similarity).
CC       ACTTS4 has the following architecture: C-A-T-C (Probable).
CC       {ECO:0000250|UniProtKB:A0A144KPJ6, ECO:0000305}.
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:18986255). The CDCs are not essential for saprophytic growth
CC       but controls host-selective pathogenicity (PubMed:18986255). Although
CC       conventional disruption of ACTT2 could not be accomplished due to the
CC       high number of the copies identified in the genome, the high sequence
CC       identity among these copies of ACTT2 is likely an advantage for RNA
CC       silencing, because it allows knockdown of all copies of this gene
CC       simultaneously (PubMed:18986255). {ECO:0000269|PubMed:18986255}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR   EMBL; LC026099; BAU45383.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A125SUR3; -.
DR   SMR; A0A125SUR3; -.
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; -; 1.
DR   Gene3D; 3.30.300.30; -; 1.
DR   Gene3D; 3.30.559.10; -; 2.
DR   InterPro; IPR010071; AA_adenyl_domain.
DR   InterPro; IPR036736; ACP-like_sf.
DR   InterPro; IPR045851; AMP-bd_C_sf.
DR   InterPro; IPR020845; AMP-binding_CS.
DR   InterPro; IPR000873; AMP-dep_Synth/Lig.
DR   InterPro; IPR023213; CAT-like_dom_sf.
DR   InterPro; IPR001242; Condensatn.
DR   InterPro; IPR020806; PKS_PP-bd.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   Pfam; PF00501; AMP-binding; 1.
DR   Pfam; PF00668; Condensation; 3.
DR   Pfam; PF00550; PP-binding; 1.
DR   SMART; SM00823; PKS_PP; 1.
DR   SUPFAM; SSF47336; SSF47336; 1.
DR   TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR   PROSITE; PS00455; AMP_BINDING; 1.
DR   PROSITE; PS50075; CARRIER; 1.
PE   3: Inferred from homology;
KW   Ligase; Phosphopantetheine; Phosphoprotein; Repeat.
FT   CHAIN           1..1507
FT                   /note="Nonribosomal peptide synthetase ACTTS4"
FT                   /id="PRO_0000444815"
FT   DOMAIN          991..1067
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          34..438
FT                   /note="Condensation 1"
FT                   /evidence="ECO:0000255"
FT   REGION          462..860
FT                   /note="Adenylation 1"
FT                   /evidence="ECO:0000255"
FT   REGION          1087..1503
FT                   /note="Condensation 2"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         1028
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   1507 AA;  167759 MW;  32EF868A401E98FA CRC64;
     MDDEIPPFSL VGRHVQDYIQ QVAGESKVDP TLIENILPCT PWQARLLTTA TEQHEGTLRA
     VLELGEDVGW SRFYAAWSKV VQAASILRTR IIKHDKYGVF QVIMKEDAAW KFSEATAKES
     DNQPVEGSFG QPLSTYAIVT DGDSRKFLWT MDRAMFDPHM IRRLTTMLSE AYHERAFAGL
     KGFDCFLKNL QDRDEAKYKA FWTMNLEGSN AFSFPTSPGP PEPTIVSRYE SPWSLLPLVS
     PKLDSSNLVH ASLAVVLGRY FGEGDIVFGA LSSQRDTSLP DADMIMGPAM TEFPIRIQVV
     QDQPVASLLE AVALESLTRR PFEHTDVSEI SNLNEDTQRG STYQTLMLLH EAENCFQDDR
     SIGTWIDETA MMFGAHPLVL QCFLVDGRVK VVANYDQNVL RSREAEALAE ALILVMRQII
     EAEPSKKVKE IDCLTPSELE RVWTWNAALP APIESCVHTL IEQQSSRQPT ALAVCAWDGN
     LTYGELESLS NRLAHYLARL DVGQGTVVPL LFEKSMWVQV AILAVLKVGC AFVLLDPSGT
     AGRRKHQLER VGGRIVLTSE RYSDLALGAH HFAVAVGSHS ASSWNALPVQ GLTCPSPSSI
     AYVIFTSGST GEPKGISVPH RSVSSSSKYH GIRAGVSPSS RVLQFASYTF DASVFEIITT
     LVFGGCVCVP SDQERLGDIS RLITSMDVNV AFLVPSVSRV LEPSEVPSLK TLIIGGEPST
     RTDLQRWAHL PTLINGYGPT ECTVFSNMHN VDLSIWNHST IGKAVGSSSW VVSQVDHTKL
     AQIGAIGELL IEGPILSHGY LRDPEKTSAS FIQDPPWLLQ GGCGYPGRRG KLYKTGDLVR
     YNDDGTLCFV RRKDEQVKIR GQRMELGEVE HYVRECVQGV VQAASEILLP AWENAKPVLA
     AFVTTIKSLN EEAKNLATYR ISAMGLGIEE SRKLAENLPE YMVPTVYFTI SRMPITASGK
     IDRKKLRDLG AEFLTQQAIE QKNTKGLIQE RSMGVTEQQI QQAWSRVLNI DSAFIGLDDN
     FFRLGGDSIS TMSLVAELRK LKIHISIDDI FNQPTLRDLA GSVTAIAPHD EGRTGGSKKD
     EMSPQAFALS PMQELFFRLQ TDPNICFDQC YLLGLEQRVS FEDVDRAFQT IIGRHAVLRT
     RFNRGMDGKW EQRIATSVSE SYVFNSVTVS GDRECAQMIS QARGKLNIMS GPLFAALLIE
     GTEEQRLFIC IHHAVMDMVS WRILLRELEQ LLLDGQLTVP PGMSFQEWCS LQDKHISESF
     APVQAADDEK PKVPRGWELA PDVDGILRIE SFVVDQRVSS KIMGMSNDAL QTKPIELMLA
     ALTSSFNLAF PDFQHPRIFV ESHGREAWDN NIDVSRTVGW FTTLFPIQVY PGSSLLETIS
     QTKDYLRGLP RRGWSYFASK FVTEQEKAAF VSKFPVDVTF NYVGMFQQLE RTDSLFKTLS
     LPENCRPVSL PQSKRLGLFE LEVSLEDGCI KVALLYPESA NTKKEVELWM GNFKEAFAEI
     AHTLASV