LOCUS       BGC0000535             15016 bp    DNA     linear   BCT 05-OCT-2011
DEFINITION  Lactococcus lactis subsp. lactis nisin biosynthetic gene cluster,
            complete sequence.
ACCESSION   BGC0000535
VERSION     BGC0000535
KEYWORDS    .
SOURCE      Lactococcus lactis subsp. lactis
  ORGANISM  Lactococcus lactis subsp. lactis
            Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
            Lactococcus.
COMMENT     ##antiSMASH-Data-START##
            Version      :: 6.2.0-924c3663(changed)
            Run date     :: 2022-11-07 19:47:45
            NOTE: This is a single region extracted from a larger record!
            Orig. start  :: 0
            Orig. end    :: 15016
            ##antiSMASH-Data-END##
FEATURES             Location/Qualifiers
     source          1..15016
                     /collected_by="John Samelis"
                     /country="Greece"
                     /db_xref="taxon:1360"
                     /isolation_source="raw milk"
                     /mol_type="genomic DNA"
                     /organism="Lactococcus lactis subsp. lactis"
                     /strain="M78"
                     /sub_species="lactis"
     protocluster    1..15016
                     /aStool="rule-based-clusters"
                     /category="RiPP"
                     /contig_edge="True"
                     /core_location="[1108:7140]"
                     /cutoff="20000"
                     /detection_rule="((LANC_like and (Lant_dehydr_N or
                     Lant_dehydr_C)) and not (YcaO or TIGR03604))"
                     /neighbourhood="10000"
                     /product="lanthipeptide-class-i"
                     /protocluster_number="1"
                     /tool="antismash"
     proto_core      1109..7140
                     /aStool="rule-based-clusters"
                     /tool="antismash"
                     /cutoff="20000"
                     /detection_rule="((LANC_like and (Lant_dehydr_N or
                     Lant_dehydr_C)) and not (YcaO or TIGR03604))"
                     /neighbourhood="10000"
                     /product="lanthipeptide-class-i"
                     /protocluster_number="1"
     cand_cluster    1..15016
                     /candidate_cluster_number="1"
                     /contig_edge="True"
                     /detection_rules="((LANC_like and (Lant_dehydr_N or
                     Lant_dehydr_C)) and not (YcaO or TIGR03604))"
                     /kind="single"
                     /product="lanthipeptide-class-i"
                     /protoclusters="1"
                     /tool="antismash"
     subregion       1..15016
                     /aStool="externally annotated by: MIBiG"
                     /contig_edge="True"
                     /label="BGC0000535"
                     /subregion_number="1"
                     /tool="antismash"
     region          1..15016
                     /candidate_cluster_numbers="1"
                     /contig_edge="True"
                     /product="lanthipeptide-class-i"
                     /region_number="1"
                     /rules="((LANC_like and (Lant_dehydr_N or Lant_dehydr_C))
                     and not (YcaO or TIGR03604))"
                     /subregion_numbers="1"
                     /tool="antismash"
     gene            828..1001
                     /gene="nisA"
     CDS             828..1001
                     /codon_start=1
                     /gene="nisA"
                     /gene_functions="biosynthetic-additional
                     (rule-based-clusters) TIGR03731"
                     /gene_functions="biosynthetic-additional
                     (rule-based-clusters) mature_a"
                     /gene_functions="biosynthetic-additional (lanthipeptides)
                     predicted lanthipeptide"
                     /gene_kind="biosynthetic-additional"
                     /note="prenisin; nisin A structural protein"
                     /product="NisA"
                     /protein_id="ADJ56352.1"
                     /sec_met_domain="TIGR03731 (E-value: 1.3e-24, bitscore:
                     75.6, seeds: 23, tool: rule-based-clusters)"
                     /sec_met_domain="mature_a (E-value: 6.5e-08, bitscore:
                     21.5, seeds: 5, tool: rule-based-clusters)"
                     /transl_table=11
                     /translation="MSTKDFNLDLVSVSKKDSGASPRITSISLCTPGCKTGALMGCNMK
                     TATCHCSIHVSK"
     CDS_motif       828..896
                     /prepeptide="leader"
                     /note="peptide class: lanthipeptide"
                     /note="predicted sequence: MSTKDFNLDLVSVSKKDSGASPR"
                     /locus_tag="nisA_lanthipeptide"
                     /aSTool="lanthipeptides"
                     /tool="antismash"
     CDS_motif       897..1001
                     /prepeptide="core"
                     /locus_tag="nisA_lanthipeptide"
                     /peptide="lanthipeptide"
                     /predicted_class="Class I"
                     /score="26.70"
                     /molecular_weight="3336.0"
                     /monoisotopic_mass="3333.6"
                     /core_sequence="ITSISLCTPGCKTGALMGCNMKTATCHCSIHVSK"
                     /aSTool="lanthipeptides"
                     /tool="antismash"
                     /leader_sequence="MSTKDFNLDLVSVSKKDSGASPR"
                     /leader_location="[827:896](+)"
                     /alternative_weights="3354.0"
                     /alternative_weights="3372.1"
                     /alternative_weights="3390.1"
                     /alternative_weights="3408.1"
     misc_feature    828..14152
                     /note="nisin biosynthetic gene cluster"
     gene            1109..4090
                     /gene="nisB"
     CDS             1109..4090
                     /codon_start=1
                     /function="dehydration of serine and threonine"
                     /gene="nisB"
                     /gene_functions="biosynthetic (rule-based-clusters)
                     lanthipeptide-class-i: Lant_dehydr_N"
                     /gene_functions="biosynthetic (rule-based-clusters)
                     lanthipeptide-class-i: Lant_dehydr_C"
                     /gene_functions="biosynthetic-additional
                     (rule-based-clusters) Lanthipeptide_LanB_RRE"
                     /gene_functions="biosynthetic-additional (smcogs)
                     SMCOG1155:Lantibiotic dehydratase domain protein (Score:
                     859.9; E-value: 3.6e-260)"
                     /gene_kind="biosynthetic"
                     /note="nisin biosynthesis protein"
                     /product="NisB"
                     /protein_id="ADJ56353.1"
                     /sec_met_domain="Lant_dehydr_N (E-value: 1.9e-87, bitscore:
                     283.3, seeds: 73, tool: rule-based-clusters)"
                     /sec_met_domain="Lant_dehydr_C (E-value: 2.8e-18, bitscore:
                     56.0, seeds: 35, tool: rule-based-clusters)"
                     /sec_met_domain="Lanthipeptide_LanB_RRE (E-value: 1e-09,
                     bitscore: 28.7, seeds: 20, tool: rule-based-clusters)"
                     /transl_table=11
                     /translation="MIKSSFKAQPFLVRNTILSPNDKRSFTEYTQVIETVSKNKVFLEQ
                     LLLANPKLYDVMQKYNAGLLKKKRVKKLFESIYKYYKRSYLRSTPFGLFSETSIGVFSK
                     SSQYKLMGKTTKGIRLDTQWLIRLVHKMEVDFSKKLSFTRNNANYKFGDRVFQVYTINS
                     SELEEVNIKYTNVYQIISEFCENDYQKYEDICETVTLCYGDEYRELSEQYLGSLIVNHY
                     LISNLQKDLLSDFSWNTFLTKVEAIDEDKKYIIPLKKVQKFIQEYSEIEIGEGIEKLKE
                     IYQEMSQILENDNYIQIDLISDSEINFDVKQKQQLEHLAEFLGNTTKSVRRTYLDDYKD
                     KFIEKYGVDQEVQITELFDSTFGIGAPYNYNHPRNDFYESEPSTLYYSEEEREKYLSMY
                     VEAVKNHNVINLDDLESHYQKMDLEKKSELQGLELFLNLAKEYEKDIFILGDIVGNNNL
                     GGASGRFSALSPELTSYHRTIVDSVERENENKEITSCEIVFLPENIRHANVMHTSIMRR
                     KVLPFFTSTSHNEVLLTNIYIGIDEKEKFYARDISTQEVLKFYITSMYNKTLFSNELRF
                     LYEISLDDKFGNLPWELIYRDFDYIPRLVFDEIVISPAKWKIWGRDVNSKMTIRELIQS
                     KEIPKEFYIVNGDNKVYLSQENPLDMEILESAIKKSSKRKDFIELQEYFEDENIINKGE
                     KGRVADVVVPFIRTRALGNEGRAFIREKRVSVERREKLPFNEWLYLKLYISINRQNEFL
                     LSYLPDIQKIVANLGGNLFFLRYTDPKPHIRLRIKCSDLFLAYGSILEILKRSRKNRIM
                     STFDISIYDQEVERYGGFDTLELSEAIFCADSKIIPNLLTLIKDTNNDWKVDDVSILVN
                     YLYLKCFFENDNKKILNFLNLVSPKKVKENVNEKIEHYLKLLKVNNLGDQIFYDKNFKE
                     LKHAIKNLFLKMIAQDFELQKVYSIIDSIIHVHNNRLIGIERDKEKLIYYTLQRLFVSE
                     EYMK"
     gene            4101..5903
                     /gene="nisT"
     CDS             4101..5903
                     /codon_start=1
                     /function="secretion of prenisin"
                     /gene="nisT"
                     /gene_functions="transport (smcogs) SMCOG1000:ABC
                     transporter ATP-binding protein (Score: 163.7; E-value:
                     9.5e-50)"
                     /gene_kind="transport"
                     /note="nisin transport ATP-binding protein"
                     /product="NisT"
                     /protein_id="ADJ56354.1"
                     /transl_table=11
                     /translation="MDEVKEFTSKQFFNTLLTLPSTLKLIFQLEKRYAIYLIVLNAITA
                     FVPLASLFIYQDLINSVLGSGRHLINIIIIYFIVQVITTVLGQLESYVSGKFDMRLSYS
                     INMRLMRTTSSLELSDYEQADMYNIIEKVTQDSTYKPFQLFNAIIVVLSSFISLLSSLF
                     FIGTWNIGVAILLLIVPVLSLVLFLRVGQLEFLIQWQRASSERETWYIVYLLTHDFSFK
                     EIKLNNISNYFIHKFGKLKKGFINQDLAIARKKTYFNIFLDFILNLINILTIFAMILSV
                     RAGKLLIGNLVSLIQAISKINTYSQTMIQNIYIIYNTSLFMEQLFEFLKRESVVHKKIE
                     DTEICNQHIGTVKVINLSYVYPNSNAFALKNINLSFEKGELTAIVGKNGSGKSTLVKII
                     SGLYQPTMGIIQYDKMRSSLMPEEFYQKNISVLFQDFVKYELTIRENIGLSDLSSQWED
                     EKIIKVLDNLGLDFLKTNNQYVLDTQLGNWFQEGHQLSGGQWQKIALARTFFKKASIYI
                     LDEPSAALDPVAEKEIFDYFVALSENNISIFISHSLNAARKANKIVVMKDGQVEDVGSH
                     DVLLRRCQYYQELYYSEQYEDNDE"
     gene            5896..7140
                     /gene="nisC"
     CDS             5896..7140
                     /codon_start=1
                     /function="cyclization, formation of (methyl)lantionines"
                     /gene="nisC"
                     /gene_functions="biosynthetic (rule-based-clusters)
                     lanthipeptide-class-i: LANC_like"
                     /gene_functions="biosynthetic-additional (smcogs)
                     SMCOG1140:Lanthionine synthetase C family protein (Score:
                     337; E-value: 2.6e-102)"
                     /gene_kind="biosynthetic"
                     /note="nisin biosynthesis protein"
                     /product="NisC"
                     /protein_id="ADJ56355.1"
                     /sec_met_domain="LANC_like (E-value: 8.3e-76, bitscore:
                     244.5, seeds: 47, tool: rule-based-clusters)"
                     /transl_table=11
                     /translation="MNKKNIKRNVEKIIAQWDERTRKNKENFDFGELTLSTGLPGIILM
                     LAELKNKDNSKIYQKKIDNYIEYIVSKLSTYGLLTGSLYSGAAGIALSILHLREDDEKY
                     KNLLDSLNRYIEYFVREKIEGFNLENITPPDYDVIEGLSGILSYLLLINDEQYDDLKIL
                     IINFLSNLTKENKGLISLYIKSENQMSQSESEMYPLGCLNMGLAHGLAGVGCILAYAHI
                     KGYSNEASLSALQKIIFIYEKFELERKKQFLWKDGLVADELKKEKVIREASFIRDAWCY
                     GGPGISLLYLYGGLALDNDYFVDKAEKILESAMQRKLGIDSYMICHGYSGLIEICSLFK
                     RLLNTKKFDSYMEEFNVNSEQILEEYGDESGTGFLEGISGCILVLSKFEYSINFTYWRQ
                     ALLLFDDFLKGGKRK"
     gene            7137..7874
                     /gene="nisI"
     CDS             7137..7874
                     /codon_start=1
                     /gene="nisI"
                     /note="nisin immunity protein; nisin-binding lipoprotein"
                     /product="NisI"
                     /protein_id="ADJ56356.1"
                     /transl_table=11
                     /translation="MRRYLILIVALIGITGLSGCYQTSHKKVRFDEGSYTNFIYDNKSY
                     FVTDKEIPQENVNNSKVKFYKLLIVDMKSEKLLSSSNKNSVTLVLNNIYEASDKSLCMG
                     INDRYYKILPESDKGAVKALRLQNFDVTSDISDDNFVIDKNDSRKIDYMGNIYSISDTT
                     VSDEELGEYQDVLAEVRVFDSVSGKSIPRSEWGRIDKDGSNSKQSRTEWDYGEIHSIRG
                     KSLTEAFAVEINDDFKLATKVGN"
     gene            7876..9924
                     /gene="nisP"
     CDS             7876..9924
                     /codon_start=1
                     /function="cleavage of leader peptide from prenisin and
                     activation of nisin"
                     /gene="nisP"
                     /gene_functions="biosynthetic-additional
                     (rule-based-clusters) Peptidase_S8"
                     /gene_functions="biosynthetic-additional (smcogs)
                     SMCOG1075:alkaline serine protease, subtilase family
                     (Score: 249.7; E-value: 1.2e-75)"
                     /gene_kind="biosynthetic-additional"
                     /note="nisin leader peptide-processing serine protease"
                     /product="NisP"
                     /protein_id="ADJ56357.1"
                     /sec_met_domain="Peptidase_S8 (E-value: 2.3e-50, bitscore:
                     161.0, seeds: 43, tool: rule-based-clusters)"
                     /transl_table=11
                     /translation="MKKILGFLFIVCSLGLSATVHGETTNSQQLLSNNINTELINHNSN
                     AILSSTEGSTTDSINLGAQSPAVKSTTRTELDVTGAAKTLLQTSAVQKEMKVSLQETQV
                     SSEFSKRDSVTNKEAVPVSKDELLEQSEVVVSTSSIQKNKILDNKKNRANFVTSSPLIK
                     EKPSNSKDASGVIDNSASPLSYRKAKEVVSLRQPLKNQKVEAQPLLISNSSEKKASVYT
                     NSHDFWDYQWDMKYVTNNGESYALYQPSKKISVGIIDSGIMEEHPDLSNSLGNYFKNLV
                     PKGGFDNEEPDETGNPSDIVDKMGHGTEVAGQITANGNILGVAPGITVNIYRVFGENLS
                     KSEWVARAIRRAADDGNKVINISAGQYLMISGSYDDGTNDYQEYLNYKSAINYATAKGS
                     IVVAALGNDSLNIQDNQTMINFLKRFRSIKVPGKVVDAPSVFEDVIAVGGIDGYGNISD
                     FSNIGADAIYAPAGTTANFKKYGQDKFVSQGYYLKDWLFTTTNTGWYQYVYGNSFATPK
                     VSGALALVVDKYGIKNPNQLKRFLLMNSPEVNGNRVLNIVDLLNGKNKAFSLDTDKGQD
                     DAINHKSMENLKESRDTMKQEQDKEIQRNTNNNFSIKNDFHNISKEVISVDYNINQKMA
                     NNRNSRGAVSVRSQEILPVTGDGEDFLPALGIVCISILGILKRKTKN"
     gene            9993..10679
                     /gene="nisR"
     CDS             9993..10679
                     /codon_start=1
                     /function="transcriptional activator/response regulator in
                     two-component regulatory system"
                     /gene="nisR"
                     /gene_functions="regulatory (smcogs) SMCOG1008:response
                     regulator (Score: 180.3; E-value: 6.6e-55)"
                     /gene_kind="regulatory"
                     /note="nisin biosynthesis regulatory protein"
                     /product="NisR"
                     /protein_id="ADJ56358.1"
                     /transl_table=11
                     /translation="MYKILIVDDDQEILKLMKTALEMRNYEVAMHQNISLPLDITDFQG
                     FDLILLDIMMSNIEGTEICKRIRREISTPIIFVSAKDTEEDIINGLGIGGDDYITKPFS
                     LKQLVAKVEANIKREERNKHAVHVFSEIRRDLGPITFYLEERRVCVNGQTIPLTCREYD
                     ILELLSQRTSKVYTREDIYDDVYDEYSNALFRSISEYIYQIRSKFAPYDINPIKTVRGL
                     GYQWHG"
     gene            10672..12015
                     /gene="nisK"
     CDS             10672..12015
                     /codon_start=1
                     /function="sensor protein in two-component regulatory
                     system"
                     /gene="nisK"
                     /gene_functions="regulatory (smcogs) SMCOG1003:sensor
                     histidine kinase (Score: 102.5; E-value: 5e-31)"
                     /gene_kind="regulatory"
                     /note="nisin biosynthesis sensor protein"
                     /product="NisK"
                     /protein_id="ADJ56359.1"
                     /transl_table=11
                     /translation="MGKKYSMRRRIWQAVIEIIIGTCLLILLLLGLTFFLRQIGQISGS
                     ETIRLSLDSDNLTISDIERDMKHYPYDYIIFDNDTSKILGGHYVKSDVPSFVASKQSSH
                     NITEGEITYTYSSNKHFSVVLRQNSMPEFTNHTLRSISYNQFTYLFFFLGEIILIIFSV
                     YHLIREFSKNFQAVQKIALKMGEITTFPEQEESKIIEFDQVLNNLYSKSKELAFLIEAE
                     RHEKHDLSFQVAALSHDVKTPLTVLKGNIELLEMTEVNEQQADFIESMKNSLTVFDKYF
                     NTMISYTKLLNDENDYKATISLEDFLIDLSVELEELSTTYQVDYQLVKKTDLTTFYGNT
                     LALSRALINIFVNACQYAKEGEKIVSLSIYDDEKYLYFEIWNNGHPFSEQAKKNAGKLF
                     FTEDTGRSGKHYGIGLSFAQGVALKHQGNLILSNPQKGGAEVILKIKK"
     gene            12114..12791
                     /gene="nisF"
     CDS             12114..12791
                     /codon_start=1
                     /function="secretion of cell-associated nisin"
                     /gene="nisF"
                     /gene_functions="transport (smcogs) SMCOG1000:ABC
                     transporter ATP-binding protein (Score: 173.7; E-value:
                     8.2e-53)"
                     /gene_kind="transport"
                     /note="nisin transport/immunity protein; component of
                     ABC-transporter"
                     /product="NisF"
                     /protein_id="ADJ56360.1"
                     /transl_table=11
                     /translation="MQVKIQNLSKTYKEKQVLQDISFDIKSGTVCGLLGVNGAGKSTLM
                     KILFGLISADTGKIFFDGQEKTNNQLGALIEAPAIYMNLSAFDNLKTKALLFGISDKRI
                     HETLEVIGLAETGKKRAGKFSLGMKQRLGIGMAILTEPQFLILDEPTNGLDPDGIAELL
                     NLILKLKAKGVTILISSHQLHEISKVASQIIILNKGKIRYNHANNKEDDIEQLFFKIVH
                     GGM"
     gene            12793..13521
                     /gene="nisE"
     CDS             12793..13521
                     /codon_start=1
                     /function="secretion of cell-associated nisin"
                     /gene="nisE"
                     /note="nisin transport/immunity protein; component of
                     ABC-transporter"
                     /product="NisE"
                     /protein_id="ADJ56361.1"
                     /transl_table=11
                     /translation="MKRIIASEAIKLKKSGTLRLVLIIPFVTLFIAFLMGGIQIFSVFS
                     IYWWETGFLFLLMSLLFLYDIKSEEQAGNFQNVKWKKLSWKIHLAKMLLIWLRGILASI
                     VLIILLYLVAFVFQGIVVVDFMKVSVALIAILLAASWNLPFIYLIFKWINTYVLLAANT
                     LICLIVAPFVAQTPVWFLLPYTYHYKVTESLLNIKPSGDLLTGKINFSIWEVLLPFGLS
                     IVVTIGVSYLLKGVIEHDKK"
     gene            13508..14152
                     /gene="nisG"
     CDS             13508..14152
                     /codon_start=1
                     /function="secretion of cell-associated nisin"
                     /gene="nisG"
                     /note="nisin transport/immunity protein; component of
                     ABC-transporter"
                     /product="NisG"
                     /protein_id="ADJ56362.1"
                     /transl_table=11
                     /translation="MIRSECLKLKNSLGFYLVFLFTLLELLTVPIYLAFGRSHVSMTDL
                     SLMIFLFFPLLVTILSILIFEQESLANRFQEINVNKKSSRIWLSKLIVVDFLLFFPSAM
                     IWIITGVSQAVGQQGMMIATASWLMAIFLNHFHLLLTFIINRGGSMIIAIIEILLIIFA
                     SNKVLLAAYWCPIALPVNFMITGRCAYLIAAVGWIVLSTIILVALSKKKIR"
ORIGIN
        1 tctcttaact ccgtgtctag tttttcgttg actttccatt atgcttggat tttttattgt
       61 ttaattccct ttttttgtat acaagctcgt attcttaaca aataattggc atatcgggtt
      121 taaaaatact atgtgtttta aagaatctct catgagtttg acgccaataa cttagattaa
      181 aatcaccgtc accttatttt taggcacgtt cggcagtaac cttatcaaag gtatctcagt
      241 cattaagttt catgatagta tttactattt tgatggttct tgttattatc caatcgttaa
      301 aatgacaaaa acaaatagat aaatagataa atatttatgg ggaggacaag tgaacttatc
      361 atgattaatt gtaaacgatt gagttctgaa tgtttcaaat tatgaggaac aacaggagtt
      421 ggactattct ttaaacgcct cgacgatacc atcactcttc attagcctaa aattaacaag
      481 ttaaaatcat tagaataatc tcttttacaa aaaatattta tttaagttat agttgacgaa
      541 tatttaataa ttttattaat atcttgattt tctagttcct gaataatata gagataggtt
      601 tattgagtct taaacatact tgaatgacct agtcttataa ctatactgac aatagaaaca
      661 ttaacaaatc taaaacagtc ttaattctat cttgagaaag tattggtaat aatattattg
      721 tcgataacgc gagcataata aacggctctg attaaattct gaagtttgtt agatacaatg
      781 atttcgttcg aaggaactac aaaataaatt ataaggaggc actcaaaatg agtacaaaag
      841 attttaactt ggatttggta tctgtttcga agaaagattc aggtgcatca ccacgcatta
      901 caagtatttc gctatgtaca cccggttgta aaacaggagc tctgatgggt tgtaacatga
      961 aaacagcaac ttgtcattgt agtattcacg taagcaaata accaaatcaa aggatagtat
     1021 tttgttagtt cagacatgga tactatccta tttttataag ttatttaggg ttgctaaata
     1081 gcttataaaa ataaagagag gaaaaaacat gataaaaagt tcatttaaag ctcaaccgtt
     1141 tttagtaaga aatacaattt tatctccaaa cgataaacgg agttttactg aatatactca
     1201 agtcattgag actgtaagta aaaataaagt ttttttggaa cagttactac tagctaatcc
     1261 taaactctat gatgttatgc agaaatataa tgctggtctg ttaaagaaga aaagggttaa
     1321 aaaattattt gaatctattt acaagtatta taagagaagt tatttacgat caactccatt
     1381 tggattattt agtgaaactt caattggtgt tttttcgaaa agttcacagt acaagttaat
     1441 gggaaagact acaaagggta taagattgga tactcagtgg ttgattcgcc tagttcataa
     1501 aatggaagta gatttctcaa aaaagttatc atttactaga aataatgcaa attataagtt
     1561 tggagatcga gtttttcaag tttataccat aaatagtagt gagcttgaag aagtaaatat
     1621 taaatatacg aatgtttatc aaattatttc tgaattttgt gagaatgact atcaaaaata
     1681 tgaagatatt tgtgaaactg taacgctttg ctatggagac gaatatagag aactatcgga
     1741 acaatatctt ggcagtctga tagttaatca ttatttgatc tctaatttac aaaaagattt
     1801 gttgtcagat ttttcttgga acactttttt gactaaagtt gaagcaatag atgaagataa
     1861 aaaatatata attcctctga aaaaagttca aaagtttatt caagaatact cagaaataga
     1921 aattggtgaa ggtattgaga aactgaaaga aatatatcag gaaatgtcac aaattcttga
     1981 gaatgataat tatattcaaa ttgatttaat tagtgatagt gaaataaatt ttgatgttaa
     2041 acaaaagcaa caattagaac atttagctga gtttttagga aatacgacaa aatctgtaag
     2101 aagaacatat ttggatgact ataaggataa atttatcgaa aaatatggtg tagatcaaga
     2161 agtacaaata acagaattat ttgattctac atttggcata ggagctccat ataattataa
     2221 tcatcctcga aatgactttt atgagtccga accgagtact ctatactatt cagaagagga
     2281 gagagaaaag tacctcagca tgtatgtaga agccgttaaa aatcataatg taattaatct
     2341 tgacgactta gagtctcatt atcaaaaaat ggacttagaa aagaaaagtg aacttcaagg
     2401 gttagaatta tttttgaatt tggcaaagga gtatgaaaaa gatattttta ttttagggga
     2461 tatcgttgga aataataatt tgggaggggc atcaggtaga ttttctgcac tctctccgga
     2521 gttaacaagt tatcatagaa cgatagtaga ttctgtcgaa agagaaaatg agaataaaga
     2581 aattacatcg tgtgaaatag tatttcttcc agaaaatatc agacatgcta acgttatgca
     2641 tacatcaatt atgaggagga aagtacttcc attttttaca agtacaagtc acaatgaagt
     2701 tctgttaact aatatctata ttggaataga cgaaaaagaa aaattttatg cacgagacat
     2761 ttcaactcaa gaggtattga aattctacat tacaagcatg tacaataaaa cgttattcag
     2821 taatgagcta agatttcttt acgaaatttc attagatgac aagtttggta atttaccttg
     2881 ggaacttatt tacagagact ttgattatat tccacgttta gtatttgacg aaatagtaat
     2941 atctcctgct aaatggaaaa tttggggaag ggatgtaaat agtaagatga caataagaga
     3001 acttattcaa agcaaagaaa ttcccaaaga gttttatatt gtcaatggag ataataaagt
     3061 ttatttatca caggaaaacc cattggatat ggaaatttta gagtcggcga taaagaagag
     3121 ctcaaaaaga aaagatttta tagagctaca agaatatttt gaagatgaaa atatcataaa
     3181 taaaggagaa aaggggagag ttgccgatgt tgtagtgcct tttattagaa cgagagcatt
     3241 aggtaatgaa gggagagcat ttataagaga gaaaagagtt tcggttgaac ggcgtgaaaa
     3301 attgcccttt aacgagtggc tttatctaaa gttgtacatt tctataaatc gtcaaaatga
     3361 atttttactg tcgtatcttc cagatattca gaaaatagta gcaaacctgg gtggaaatct
     3421 attcttccta agatatactg atcctaaacc acatattaga ttgcgtataa aatgttcaga
     3481 tttattttta gcttacggat ctattcttga aatcttaaaa aggagtcgga aaaataggat
     3541 aatgtcaact tttgatattt ctatttatga tcaagaagta gaaagatatg gtggatttga
     3601 tactttagag ttatccgaag caatattttg tgccgattct aaaattattc caaatttgct
     3661 tacattgata aaagatacta ataatgattg gaaagtcgat gatgtatcaa tcttggtgaa
     3721 ttatttatat ctgaaatgct tctttgagaa tgataacaaa aagattctta attttttgaa
     3781 tttagttagt cctaaaaagg ttaaagaaaa tgtcaatgaa aagattgaac attatcttaa
     3841 gcttctgaaa gttaataatc taggtgacca aattttttat gacaagaatt ttaaagaatt
     3901 aaagcatgcc ataaaaaatt tatttttaaa aatgatagct caagattttg aacttcagaa
     3961 agtttattca attattgaca gtatcattca tgtccataat aaccgactaa ttggtattga
     4021 acgagataaa gagaaattaa tttattacac acttcaaagg ttgtttgttt cggaagaata
     4081 catgaaatga ggactaatag atggatgaag tgaaagaatt cacatcaaaa caatttttta
     4141 atactttact tactcttcca agcaccttga agttaatttt tcagttggaa aaacgttatg
     4201 caatttattt aattgtgcta aatgctatca cagcttttgt tccgttggct agtcttttta
     4261 tttatcaaga tttaataaac tctgtgctag gttcagggag acatcttatc aatattatta
     4321 tcatctattt tattgttcaa gtgataacaa cagttctggg acagctggaa agttatgtta
     4381 gtggaaaatt tgatatgcga ctttcttaca gtatcaatat gcgcctcatg aggactacct
     4441 catctcttga attaagtgat tatgagcagg ctgatatgta taatatcata gaaaaagtta
     4501 ctcaagacag cacttacaag ccttttcagc tatttaatgc tatcattgtt gtgctttcat
     4561 cgtttatctc attgttatct agtctatttt ttattggaac atggaacatt ggggtagcaa
     4621 ttttactcct tattgttcca gtattatctt tggtactttt tctcagagtg ggacaattag
     4681 agtttttaat ccagtggcag agagcaagtt ctgaaagaga aacatggtat attgtatatt
     4741 tattgactca tgatttttca tttaaagaaa tcaagttaaa taatattagc aattacttca
     4801 ttcataaatt tggaaaatta aagaaaggat ttatcaacca agatttagct attgctcgta
     4861 agaagacata tttcaatatt tttcttgatt tcattttgaa tttgataaat attcttacga
     4921 tatttgctat gatcctttcg gtaagagcag gaaaacttct tataggtaat ttggtaagtc
     4981 tcatacaagc tatttctaaa atcaatactt attctcaaac aatgattcaa aatatttaca
     5041 tcatttataa tactagtttg tttatggaac aactttttga gtttttaaag agagaaagtg
     5101 tagttcacaa aaaaatagaa gatactgaaa tatgcaatca acatatagga actgttaaag
     5161 taattaattt atcatatgtt taccctaatt cgaatgcctt tgcactaaag aatatcaatt
     5221 tatcctttga aaaaggagaa ttaactgcta ttgtaggaaa aaatggttca gggaaaagta
     5281 cactagtaaa gataatttca ggattatatc aaccaactat gggaataatc caatacgaca
     5341 aaatgagaag tagtttgatg cctgaggagt tttatcagaa aaacatatcg gtgctgttcc
     5401 aagattttgt gaagtatgag ttaacgataa gagagaatat aggattgagt gatttgtctt
     5461 ctcaatggga agatgagaaa attattaaag tactagataa tttaggactc gattttttga
     5521 aaactaataa tcaatatgta cttgatacgc agttaggaaa ttggtttcaa gaagggcatc
     5581 aactttcagg aggtcagtgg caaaaaattg cattagcaag gacattcttt aagaaagctt
     5641 caatttatat tttagatgaa ccaagtgctg cactcgatcc tgtagctgaa aaagaaatat
     5701 ttgattattt tgttgctctt tcggaaaata atatttcaat tttcatttct catagtttga
     5761 atgctgccag aaaagcaaat aaaatcgtgg ttatgaaaga tggacaggtc gaagatgttg
     5821 gaagtcatga tgtccttctg agaagatgtc aatactatca agaactttat tattcagagc
     5881 aatatgagga taatgatgaa taaaaaaaat ataaaaagaa atgttgaaaa aattattgct
     5941 caatgggatg agagaactag aaaaaataaa gaaaacttcg atttcggaga gttgactctc
     6001 tctacaggat tgcctggtat aattttaatg ttagcggagt taaaaaataa agataactca
     6061 aagatatatc agaaaaagat agacaattat attgaatata ttgttagcaa actttcaaca
     6121 tatgggcttt taacaggatc actttattcg ggagcagctg gcattgcatt aagtatccta
     6181 catttacgag aagatgacga aaaatataag aatcttcttg atagcctaaa tagatatatc
     6241 gaatatttcg tcagagaaaa aattgaagga tttaatttgg aaaacattac tcctcctgat
     6301 tatgacgtga ttgaaggttt atctgggata ctttcctatc tattattaat caacgacgag
     6361 caatatgatg atttgaaaat actcattatc aattttttat caaatctgac taaagaaaac
     6421 aaaggactaa tatcgcttta catcaaatcg gagaatcaga tgtctcaatc agaaagtgag
     6481 atgtatccac taggctgttt gaatatggga ttagcacatg gacttgctgg agtgggctgt
     6541 atcttagctt atgcccacat aaaaggatat agtaatgaag cctcgttgtc agctttgcaa
     6601 aaaattattt ttatttatga aaagtttgaa cttgaaagga aaaaacagtt tctatggaaa
     6661 gatggacttg tagcagatga attaaaaaaa gagaaagtaa ttagggaagc aagtttcatt
     6721 agagatgcat ggtgctatgg aggtccaggt attagtctgc tatacttata cggaggatta
     6781 gcactggata atgactattt tgtagataaa gcagaaaaaa tattagagtc agctatgcaa
     6841 aggaaacttg gtattgattc atatatgatt tgccatggct attctggttt aatagaaatt
     6901 tgttctttat ttaagcggct attaaataca aaaaagtttg attcatacat ggaagaattt
     6961 aatgttaata gtgagcaaat tcttgaagaa tacggagatg aaagtggcac gggttttctt
     7021 gaaggaataa gtggctgtat actggtatta tcgaaatttg aatattcaat caattttact
     7081 tattggagac aagcactgtt actttttgac gattttttga aaggagggaa gaggaaatga
     7141 gaagatattt aatacttatt gtggccttaa tagggataac aggtttatca gggtgttatc
     7201 aaacaagtca taaaaaggtg aggtttgacg aaggaagtta tactaatttt atttatgata
     7261 ataaatcgta tttcgtaact gataaggaga ttcctcagga gaacgttaac aattccaaag
     7321 taaaatttta taagctgttg attgttgaca tgaaaagtga gaaactttta tcaagtagca
     7381 acaaaaatag tgtgactttg gtcttaaata atatttatga ggcttctgac aagtcgctat
     7441 gtatgggtat taacgacaga tactataaga tacttccaga aagtgataag ggggcggtca
     7501 aagctttgag attacaaaac tttgatgtga caagcgatat ttctgatgat aattttgtta
     7561 ttgataaaaa tgattcacga aaaattgact atatgggaaa tatttacagt atatcggaca
     7621 ccaccgtatc tgatgaagaa ttgggagaat atcaggatgt tttagctgaa gtacgtgtgt
     7681 ttgattcagt tagtggcaaa agtatcccga ggtctgaatg ggggagaatt gataaggatg
     7741 gttcaaattc caaacagagt aggacggaat gggattatgg cgaaatccat tctattagag
     7801 gaaaatctct tactgaagca tttgccgttg agataaatga tgattttaag cttgcaacga
     7861 aggtaggaaa ctagagtgaa aaaaatacta ggtttccttt ttatcgtttg ttcgttgggt
     7921 ttatcagcaa ctgtgcatgg ggagacaaca aattcacaac agttactctc aaataatatt
     7981 aatacggaat taattaatca taattctaat gcaattttat cttcaacaga gggatcaacg
     8041 actgattcga ttaatctagg ggcgcagtca cctgcagtaa aatcgacaac aaggactgaa
     8101 ttggatgtaa ctggtgctgc taaaacttta ttacagacat cagctgttca aaaagaaatg
     8161 aaagtttcgt tgcaagaaac tcaagttagt tctgaattca gtaagagaga tagcgttaca
     8221 aataaagaag cagttccagt atctaaggat gagctacttg agcaaagtga agtagtcgtt
     8281 tcaacatcat cgattcaaaa aaataaaatc ctcgataata agaagaatag agctaacttc
     8341 gttacttcct ctccgcttat taaggaaaaa ccatcaaatt ctaaagatgc atctggtgta
     8401 attgataatt ctgcttctcc tctatcttat cgtaaagcta aggaagtggt atctcttaga
     8461 caacctttaa aaaatcaaaa agtagaggca caacctctat tgataagtaa ttcttctgaa
     8521 aagaaagcaa gtgtttatac aaattcacat gatttttggg attatcagtg ggatatgaaa
     8581 tatgtgacaa ataatggaga aagctatgcg ctctaccagc cctcaaagaa aatttctgtt
     8641 ggaattattg attcaggaat catggaagaa catcctgatt tgtcaaatag tttaggaaat
     8701 tattttaaaa atcttgttcc taagggaggg tttgataatg aagaacctga tgaaactgga
     8761 aatccaagtg atattgtcga caaaatggga cacgggacgg aagtcgcagg tcagattaca
     8821 gcaaatggta atattttagg agtagcacca gggattactg taaatatata cagagtattt
     8881 ggtgaaaatc tttcgaaatc ggaatgggta gctagagcaa taagaagagc tgcggatgat
     8941 gggaacaagg tcatcaatat aagtgctgga cagtatctta tgatttcagg atcgtatgat
     9001 gatggaacaa atgattatca agagtatctt aattataagt cagcaataaa ttatgcaaca
     9061 gcaaaaggaa gtattgttgt cgcagctctt ggtaatgata gtttaaacat acaagataac
     9121 caaacaatga taaactttct taagcgtttc agaagtataa aggttcctgg aaaagttgta
     9181 gatgcaccga gtgtatttga ggatgtaata gccgtaggtg gaatagatgg ttatggtaat
     9241 atttctgatt ttagtaatat tggagcggat gcaatttatg ctcctgctgg cacaacggcc
     9301 aattttaaaa aatatgggca agataaattt gtcagtcagg gttattattt gaaagattgg
     9361 ctttttacaa ctactaatac tggctggtac caatatgttt atggcaactc atttgctact
     9421 cctaaagtat ctggggcact ggcattagta gttgataaat atggaataaa gaatcctaac
     9481 caactaaaaa ggtttcttct aatgaattct ccagaagtta atgggaatag agtattgaat
     9541 attgttgatt tattgaatgg gaaaaataaa gcttttagct tagatacaga taaaggtcag
     9601 gatgatgcta ttaaccataa atcgatggag aatcttaaag agtctaggga tacaatgaaa
     9661 caggaacaag ataaagaaat tcaaagaaat acaaataaca atttttctat caaaaatgat
     9721 tttcataaca tttcaaaaga agtaatttca gttgattata atattaatca aaaaatggct
     9781 aataatcgaa attcgagagg tgctgtttct gtacgaagtc aagaaatttt acctgttact
     9841 ggagatggag aagatttttt accggcttta ggtatagtgt gtatctcaat ccttggtata
     9901 ttgaaaagaa agactaaaaa ttgatagatt atatttcttc agaatgaatg gtataatgaa
     9961 gtaatgagta ctaaacaatc ggaggtaaag tggtgtataa aattttaata gttgatgatg
    10021 atcaggaaat tttaaaatta atgaagacag cattagaaat gagaaactat gaagttgcga
    10081 tgcatcaaaa catttcactt cccttggata ttactgattt tcagggattt gatttgattt
    10141 tgttagatat catgatgtca aatattgaag ggacagaaat ttgtaaaagg attcgcagag
    10201 aaatatcaac tccaattatc tttgttagtg cgaaagatac agaagaggat attataaacg
    10261 gcttaggtat tggtggggat gactatatta ctaagccttt tagccttaaa cagttggttg
    10321 caaaagtgga agcaaatata aagcgagagg aacgcaataa acatgcagtt catgtttttt
    10381 cagagattcg tagagattta ggaccaatta cattttattt agaagaaagg cgagtctgtg
    10441 tcaatggtca aacaattcca ctgacttgtc gtgaatacga tattcttgaa ttactatcac
    10501 aacgaacttc taaagtttat acgagagagg atatttatga tgacgtatat gatgaatatt
    10561 ctaatgcact ttttcggtca atctcggaat atatttatca gattaggagt aagtttgcac
    10621 catacgatat taatccgata aaaacggttc ggggacttgg gtatcagtgg catgggtaaa
    10681 aaatattcaa tgcgtcgacg gatatggcaa gctgtcattg aaattatcat aggtacttgt
    10741 ctacttatcc tgttgttact gggcttgact ttctttctac gacaaattgg acaaatcagt
    10801 ggttcagaaa ctattcgttt atctttagat tcagataatt taactatttc tgatatcgaa
    10861 cgtgatatga aacactaccc atatgattat attatttttg acaatgatac aagtaaaatt
    10921 ttgggaggac attatgtcaa gtcggatgta cctagttttg tagcttcaaa acagtcttca
    10981 cataatatta cagaaggaga aattacttat acttattcaa gcaataagca tttttcagtt
    11041 gttttaagac aaaacagtat gcctgaattt acaaatcata cgcttcgttc aatttcttat
    11101 aatcaattta cttacctttt cttttttctt ggtgaaataa tactcattat tttttctgtc
    11161 tatcatctca ttagagaatt ttctaagaat tttcaagccg ttcaaaagat tgcattgaag
    11221 atgggggaaa taactacttt tcctgaacaa gaggaatcaa aaattattga atttgatcag
    11281 gttctgaata acttatattc gaaaagtaag gagttagctt tccttattga agcggagcgt
    11341 catgaaaaac atgatttatc cttccaggtt gctgcacttt cacatgatgt taagacacct
    11401 ttaacagtat taaaaggaaa tattgaactg ctagagatga ctgaagtaaa tgaacaacaa
    11461 gctgatttta ttgagtcaat gaaaaatagt ttgactgttt ttgacaagta ttttaacaca
    11521 atgattagtt atacaaaact tttgaatgat gaaaatgatt acaaagcgac aatctccctg
    11581 gaggattttt tgatagattt atcagttgag ttggaagagt tgtcaacaac ttatcaagtg
    11641 gattatcagc tagttaaaaa aacagattta accacttttt acggaaatac attagcttta
    11701 agtcgagcac ttatcaatat ctttgttaat gcctgtcagt atgctaaaga gggtgaaaaa
    11761 atagtcagtt tgagtattta tgatgatgaa aaatatctct attttgaaat ctggaataat
    11821 ggtcatcctt tttctgaaca agcaaaaaaa aatgctggaa aactattttt cacagaagat
    11881 actggacgta gtgggaaaca ctatgggatt ggactatctt ttgctcaagg tgtagcttta
    11941 aaacatcaag gaaacttaat tctcagtaat cctcaaaaag gtggggcaga agttatccta
    12001 aaaataaaaa agtaatttag taatctctaa ggattacttt ttttgtttct gaatagattc
    12061 tgaaaattgt tttatatact ttttttaaac ataaaataaa gtgaggaaat ataatgcagg
    12121 taaaaattca aaatctttct aaaacatata aagaaaagca ggtgctacaa gatatcagtt
    12181 ttgatattaa atctggaaca gtctgtggtt tattaggagt taacggtgca ggaaaatcaa
    12241 ctttgatgaa aattttgttt ggtttaattt ctgcagatac tggaaaaatt ttttttgatg
    12301 gacaagaaaa gacaaataat caacttggag ccttaatcga ggctccagca atatatatga
    12361 atttatctgc tttcgataat cttaaaacta aggctttgct ttttggaatt tcagataaga
    12421 gaattcatga aactctagaa gtgattggtt tggcagaaac aggaaagaaa agagcaggaa
    12481 aattctcttt agggatgaaa caacgtttgg gaattggtat ggctattctt acagaacctc
    12541 aatttttaat tcttgatgaa cctactaatg gtttggatcc tgatggtatt gcggagttgt
    12601 taaacttaat cttaaaactt aaagctaaag gtgtgacaat cttgatttct agtcatcagt
    12661 tgcacgaaat aagtaaagta gctagtcaaa ttattatttt gaacaaaggt aagattcgtt
    12721 ataatcatgc gaacaataaa gaagacgaca ttgaacagtt attctttaag attgtgcatg
    12781 gaggaatgtg atatgaaaag aataatagca tcagaagcaa taaaattaaa aaaatcagga
    12841 actcttagat tggtattaat tatccctttt gtgactctat ttatagcatt tcttatgggt
    12901 ggaatacaga tttttagtgt tttttcaatt tattggtggg aaactggttt tttattcctt
    12961 ttgatgagtt tgctttttct ttatgatata aaatcagagg agcaagctgg aaattttcaa
    13021 aatgtgaaat ggaaaaagct gagttggaaa attcatttgg ccaaaatgtt gttgatttgg
    13081 ctaagaggta tactagcgag catagtcttg attattttgc tttatttggt tgcttttgtg
    13141 tttcaaggta ttgtagtggt ggattttatg aaagtaagtg tggcattgat tgctatatta
    13201 ctagcagctt cttggaattt accctttata tacttgattt tcaagtggat taatacttac
    13261 gtattgttag ctgcgaatac cttgatttgt ttaattgttg ccccttttgt tgcacaaact
    13321 ccagtatggt tcttgctacc atacacttat cactataaag ttacagaaag tttgttaaat
    13381 atcaaaccat caggagattt gttaacaggg aagataaatt tcagtatttg ggaagtttta
    13441 ttaccatttg gactttccat agttgtaacg ataggagttt cgtatttact taaaggagtg
    13501 atagaacatg ataagaagtg aatgtctcaa attaaaaaat agcttagggt tttatttagt
    13561 ttttctcttt actttattag agcttttaac ggttcctatt tatttagctt ttggaagaag
    13621 tcatgtttca atgactgatt tatcgctcat gatttttttg ttttttccgt tactggttac
    13681 aattttgtct attctaatct ttgaacagga gagtctggcc aatcgtttcc aagaaataaa
    13741 tgtaaataaa aaaagtagca gaatttggtt atcaaagcta atagtagtgg atttcctttt
    13801 gttctttcca tcagcaatga tctggataat tacgggagtt tcacaggcag tagggcaaca
    13861 aggaatgatg atcgcaacag ctagctggtt gatggcaatt tttcttaatc attttcatct
    13921 tttattgacc tttataatca atcgaggagg gagcatgatt atcgcgatta ttgaaatatt
    13981 actcattatt tttgccagta ataaagtttt attagcagct tattggtgtc ccattgcttt
    14041 acctgttaat tttatgataa ctgggcggtg tgcttatctg atagctgccg tagggtggat
    14101 tgttttatcc acaataattc ttgtagcatt atctaaaaaa aagattagat aaagtatttt
    14161 ttcttatggt aattcgacct aatatgtttt tgctatttat ctcttatttc tgtctatagt
    14221 aatttattca aagtaccttt agactcataa gtttgaataa aatttccatc aatatgtgac
    14281 agttcttact ctaagaataa tgtttccgtc gttagttttc ttttctcagt aattttttat
    14341 aaagtggttt cctatcgact tacacttttt cttttggagt tattggtgtc aagctcatga
    14401 gagattcttt aaagcatata acatttttaa actgatatgc cagttatttg tgaagaatat
    14461 gagtttctat ataaaagaga aaattaaaca atgaaaaatc caagtataaa tacttggatt
    14521 tttcattatt tttgatagac atataaagtg cattttaacc tagaattaaa agatgtatcg
    14581 ttgataataa taaaatgaac caaagcaaaa ctgacgttaa gtcaatttat tagagtcaaa
    14641 aacgtataat tttaatgtat ttattttaag tgatttcttt ttcaaattga ttaggcgtaa
    14701 gataccctaa actttgatgg attcgttttg aattataaaa ggcttcaata taccagaaaa
    14761 tactctgata ggcttcttca aagttcttat atttaaattg atagacccac tctcttttta
    14821 aatgtccatg ccaagattca agactggcat tatgataagg atagccctta cgactgaagg
    14881 agtgagtcat tccagagttt tttattgtct cttcatactc atgactcgta tactgacttc
    14941 cttggtcaga atgaagcatc acagcttctg gataattttg tgattccatt gccttattca
    15001 aagtcctttg cactaa
//
