                         SEQUENCE LISTING

<110>  Novartis AG
 
<120>  PROCESS FOR PREPARING TETRAHYDROISOQUINOLINE DERIVATIVES AND 
       THEIR DERIVATIVES

<130>  PAT058187-WO-PCT02

<160>  12    

<170>  PatentIn version 3.5

<210>  1
<211>  1701
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  SEQ ID NO: 1 - PAL-124 DNA sequence - Variant of Phenylalanine Ammonia Lyase from Anabaena variabilis



<400>  1
atgaaacctt tgccgcagga tcagagcaaa accagcagcc agcagtttag ctttaccggc       60

aatagcagcg caaatgtgat tattggtaat cagaaactga ccatcaatga tgttgtacgt      120

gttgcccgta atggcaccct ggttagcctg accaataata ccgatattct gcagggtatt      180

caggccagct gtgattatat caataatgca gttgaaagcg gtgaaatgat ttatggtgtg      240

accagcggct ttggtggtat ggcaaatgtt gtaattagcc gtgaacaggc cagcgaactg      300

cagatgaatg cgatttgggc ccttaaaacc ggcgcaggta ataaactgcc gctggcagat      360

gttcgtgcag caatgctgct gcgtgcaaat agccacatgc gtggtgcaag cggtattcgt      420

ctggaactga ttaaacgcat ggaaatcttt ctgaatgccg gtgttacccc gtatgtttat      480

gaatttggta gcattggtgc cagcggtgat ctggtcccgg gatcgtatat taccggtagc      540

ctgattggtc tggacccgag ctttaaagtt gattttaatg gcaaagaaat ggacgcaccg      600

accgcactgc gtcagctgaa tctgagtccg ctgaccctgc tgccgaagga aggctgcagc      660

atggtaaatg gcaccagcgt tatgaccggt attgcagcaa attgtgttta tgatacccag      720

attctgaccg caattgcaat gggtgttcat gcactggata ttcaggcact gaatggtaca      780

aatcagagct ttcatccgtt tatccataac agcaaaccgc atccgggtca gctgtgggca      840

gcagatcaga tgattagcct gctggccggt agccagctgg ttcgtgatga actggatggt      900

aaacatgatt ggcgtgatgg cgaactgatt caggatcgtt atagcctgcg ttgtctgccg      960

cagtatctgg gtccgattgt tgatggtatt agccagattg ccaaacaaat cgaaattgag     1020

attaacagcg ttaccgataa cccgctgatt gatgttgata atcaggcaag ctattatggt     1080

ggtaattttc tgggtcagta tgttggtatg ggtatggatc atctgcgcta ttatatcggt     1140

ctgctggcaa aacatctgga tgttcagatt gcactgctga actcaccgga atttagcaat     1200

ggtctgcctc cgagtctggt gggtaataga gaacgtaaag ttaatatggg tctgaaaggc     1260

actcagattg taggtaatag cattatgccg ctgctgacct tttatggtaa tagtattgca     1320

gatcgttttc cgacccatgc cgaacagttt aaccagaata ttaacagcca gggttatacc     1380

agcgcaaccc tggcacgtcg tagcgttgat atttttcaga attatgttgc cattgccctg     1440

atgtttggtg ttcaggcagt tgatctgcgt acctacaaaa aaaccggtca ttatgatgca     1500

cgtgcatgtc tgtcaccggc aaccgaacgt ctgtatagcg cagttcgtca tgttgttggt     1560

cagaaaccga gctcagatcg tccgtatatt tggaatgata atgaacaggg tctggatgaa     1620

catattgcac gtattagtgc agatattgca gccggtggtg ttattgttca ggccgttcag     1680

gacattctgc cgtgtggaca t                                               1701


<210>  2
<211>  567
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  SEQ ID NO: 2 - PAL-124 protein sequence - Variant of Phenylalanine Ammonia Lyase from Anabaena variabilis



<400>  2

Met Lys Pro Leu Pro Gln Asp Gln Ser Lys Thr Ser Ser Gln Gln Phe 
1               5                   10                  15      


Ser Phe Thr Gly Asn Ser Ser Ala Asn Val Ile Ile Gly Asn Gln Lys 
            20                  25                  30          


Leu Thr Ile Asn Asp Val Val Arg Val Ala Arg Asn Gly Thr Leu Val 
        35                  40                  45              


Ser Leu Thr Asn Asn Thr Asp Ile Leu Gln Gly Ile Gln Ala Ser Cys 
    50                  55                  60                  


Asp Tyr Ile Asn Asn Ala Val Glu Ser Gly Glu Met Ile Tyr Gly Val 
65                  70                  75                  80  


Thr Ser Gly Phe Gly Gly Met Ala Asn Val Val Ile Ser Arg Glu Gln 
                85                  90                  95      


Ala Ser Glu Leu Gln Met Asn Ala Ile Trp Ala Leu Lys Thr Gly Ala 
            100                 105                 110         


Gly Asn Lys Leu Pro Leu Ala Asp Val Arg Ala Ala Met Leu Leu Arg 
        115                 120                 125             


Ala Asn Ser His Met Arg Gly Ala Ser Gly Ile Arg Leu Glu Leu Ile 
    130                 135                 140                 


Lys Arg Met Glu Ile Phe Leu Asn Ala Gly Val Thr Pro Tyr Val Tyr 
145                 150                 155                 160 


Glu Phe Gly Ser Ile Gly Ala Ser Gly Asp Leu Val Pro Gly Ser Tyr 
                165                 170                 175     


Ile Thr Gly Ser Leu Ile Gly Leu Asp Pro Ser Phe Lys Val Asp Phe 
            180                 185                 190         


Asn Gly Lys Glu Met Asp Ala Pro Thr Ala Leu Arg Gln Leu Asn Leu 
        195                 200                 205             


Ser Pro Leu Thr Leu Leu Pro Lys Glu Gly Cys Ser Met Val Asn Gly 
    210                 215                 220                 


Thr Ser Val Met Thr Gly Ile Ala Ala Asn Cys Val Tyr Asp Thr Gln 
225                 230                 235                 240 


Ile Leu Thr Ala Ile Ala Met Gly Val His Ala Leu Asp Ile Gln Ala 
                245                 250                 255     


Leu Asn Gly Thr Asn Gln Ser Phe His Pro Phe Ile His Asn Ser Lys 
            260                 265                 270         


Pro His Pro Gly Gln Leu Trp Ala Ala Asp Gln Met Ile Ser Leu Leu 
        275                 280                 285             


Ala Gly Ser Gln Leu Val Arg Asp Glu Leu Asp Gly Lys His Asp Trp 
    290                 295                 300                 


Arg Asp Gly Glu Leu Ile Gln Asp Arg Tyr Ser Leu Arg Cys Leu Pro 
305                 310                 315                 320 


Gln Tyr Leu Gly Pro Ile Val Asp Gly Ile Ser Gln Ile Ala Lys Gln 
                325                 330                 335     


Ile Glu Ile Glu Ile Asn Ser Val Thr Asp Asn Pro Leu Ile Asp Val 
            340                 345                 350         


Asp Asn Gln Ala Ser Tyr Tyr Gly Gly Asn Phe Leu Gly Gln Tyr Val 
        355                 360                 365             


Gly Met Gly Met Asp His Leu Arg Tyr Tyr Ile Gly Leu Leu Ala Lys 
    370                 375                 380                 


His Leu Asp Val Gln Ile Ala Leu Leu Asn Ser Pro Glu Phe Ser Asn 
385                 390                 395                 400 


Gly Leu Pro Pro Ser Leu Val Gly Asn Arg Glu Arg Lys Val Asn Met 
                405                 410                 415     


Gly Leu Lys Gly Thr Gln Ile Val Gly Asn Ser Ile Met Pro Leu Leu 
            420                 425                 430         


Thr Phe Tyr Gly Asn Ser Ile Ala Asp Arg Phe Pro Thr His Ala Glu 
        435                 440                 445             


Gln Phe Asn Gln Asn Ile Asn Ser Gln Gly Tyr Thr Ser Ala Thr Leu 
    450                 455                 460                 


Ala Arg Arg Ser Val Asp Ile Phe Gln Asn Tyr Val Ala Ile Ala Leu 
465                 470                 475                 480 


Met Phe Gly Val Gln Ala Val Asp Leu Arg Thr Tyr Lys Lys Thr Gly 
                485                 490                 495     


His Tyr Asp Ala Arg Ala Cys Leu Ser Pro Ala Thr Glu Arg Leu Tyr 
            500                 505                 510         


Ser Ala Val Arg His Val Val Gly Gln Lys Pro Ser Ser Asp Arg Pro 
        515                 520                 525             


Tyr Ile Trp Asn Asp Asn Glu Gln Gly Leu Asp Glu His Ile Ala Arg 
    530                 535                 540                 


Ile Ser Ala Asp Ile Ala Ala Gly Gly Val Ile Val Gln Ala Val Gln 
545                 550                 555                 560 


Asp Ile Leu Pro Cys Gly His 
                565         


<210>  3
<211>  1701
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  SEQ ID NO: 3 - PAL-126 DNA sequence - Variant of Phenylalanine Ammonia Lyase from Anabaena variabilis



<400>  3
atgaaacctt tgccacagga tcagagcaaa accagcagcc agcagtttag ctttaccggc       60

aatagcagcg caaatgtgat tattggtaat cagaaactga ccatcaatga tgttgtacgt      120

gttgcccgta atggcaccct ggttagcctg accaataata ccgatattct gcagggtatt      180

caggccagct gtgattatat caataatgca gttgaaagcg gtgaaatgat ttatggtgtg      240

accagcggcc ctggtggtat ggcaaatgtt gtaattagcc gtgaacaggc cagcgaactg      300

cagatgaatg cgatttgggc ccttaaaacc ggcgcaggta ataaactgcc gctggcagat      360

gttcgtgcag caatgctgct gcgtgcaaat agccacatgc gtggtgcaag cggtattcgt      420

ctggaactga ttaaacgcat ggaaatcttt ctgaatgccg gtgttacccc gtatgtttat      480

gaatttggta gcattggtgc cagcggtgat ctggtcccgg gatcgtatat taccggtagc      540

ctgattggtc tggacccgag ctttaaagtt gattttaatg gcaaagaaat ggacgcaccg      600

accgcactgc gtcagctgaa tctgagtccg ctgaccctgc tgccgaagga aggctgcagc      660

atggtaaatg gcaccagcgt tatgaccggt attgcagcaa attgtgttta tgatacccag      720

attctgaccg caattgcaat gggtgttcat gcactggata ttcaggcact gaatggtaca      780

aatcagagct ttcatccgtt tatccataac agcaaaccgc atccgggtca gctgtgggca      840

gcagatcaga tgattagcct gctggccggt agccagctgg ttcgtgatga actggatggt      900

aaacatgatt ggcgtgatgg cgaactgatt caggatcgtt atagcctgcg ttgtctgccg      960

cagtatctgg gtccgattgt tgatggtatt agccagattg ccaaacaaat cgaaattgag     1020

attaacagcg ttaccgataa cccgctgatt gatgttgata atcaggcaag ctattatggt     1080

ggtaattttc tgggtcagta tgttggtatg ggtatggatc atctgcgcta ttatatcggt     1140

ctgctggcaa aacatctgga tgttcagatt gcactgctga actcaccgga atttagcaat     1200

ggtctgcctc cgagtctggt gggtaataga gaacgtaaag ttaatatggg tctgaaaggc     1260

actcagattg taggtaatag cattatgccg ctgctgacct tttatggtaa tagtattgca     1320

gatcgttttc cgacccatgc cgaacagttt aaccagaata ttaacagcca gggttatacc     1380

agcgcaaccc tggcacgtcg tagcgttgat atttttcaga attatgttgc cattgccctg     1440

atgtttggtg ttcaggcagt tgatctgcgt acctacaaaa aaaccggtca ttatgatgca     1500

cgtgcatgtc tgtcaccggc aaccgaacgt ctgtatagcg cagttcgtca tgttgttggt     1560

cagaaaccga gctcagatcg tccgtatatt tggaatgata atgaacaggg tctggatgaa     1620

catattgcac gtattagtgc agatattgca gccggtggtg ttattgttca ggccgttcag     1680

gacattctgc cgtgtggaca t                                               1701


<210>  4
<211>  567
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  SEQ ID NO: 4 - PAL-126 protein sequence - Variant of Phenylalanine Ammonia Lyase from Anabaena variabilis



<400>  4

Met Lys Pro Leu Pro Gln Asp Gln Ser Lys Thr Ser Ser Gln Gln Phe 
1               5                   10                  15      


Ser Phe Thr Gly Asn Ser Ser Ala Asn Val Ile Ile Gly Asn Gln Lys 
            20                  25                  30          


Leu Thr Ile Asn Asp Val Val Arg Val Ala Arg Asn Gly Thr Leu Val 
        35                  40                  45              


Ser Leu Thr Asn Asn Thr Asp Ile Leu Gln Gly Ile Gln Ala Ser Cys 
    50                  55                  60                  


Asp Tyr Ile Asn Asn Ala Val Glu Ser Gly Glu Met Ile Tyr Gly Val 
65                  70                  75                  80  


Thr Ser Gly Pro Gly Gly Met Ala Asn Val Val Ile Ser Arg Glu Gln 
                85                  90                  95      


Ala Ser Glu Leu Gln Met Asn Ala Ile Trp Ala Leu Lys Thr Gly Ala 
            100                 105                 110         


Gly Asn Lys Leu Pro Leu Ala Asp Val Arg Ala Ala Met Leu Leu Arg 
        115                 120                 125             


Ala Asn Ser His Met Arg Gly Ala Ser Gly Ile Arg Leu Glu Leu Ile 
    130                 135                 140                 


Lys Arg Met Glu Ile Phe Leu Asn Ala Gly Val Thr Pro Tyr Val Tyr 
145                 150                 155                 160 


Glu Phe Gly Ser Ile Gly Ala Ser Gly Asp Leu Val Pro Gly Ser Tyr 
                165                 170                 175     


Ile Thr Gly Ser Leu Ile Gly Leu Asp Pro Ser Phe Lys Val Asp Phe 
            180                 185                 190         


Asn Gly Lys Glu Met Asp Ala Pro Thr Ala Leu Arg Gln Leu Asn Leu 
        195                 200                 205             


Ser Pro Leu Thr Leu Leu Pro Lys Glu Gly Cys Ser Met Val Asn Gly 
    210                 215                 220                 


Thr Ser Val Met Thr Gly Ile Ala Ala Asn Cys Val Tyr Asp Thr Gln 
225                 230                 235                 240 


Ile Leu Thr Ala Ile Ala Met Gly Val His Ala Leu Asp Ile Gln Ala 
                245                 250                 255     


Leu Asn Gly Thr Asn Gln Ser Phe His Pro Phe Ile His Asn Ser Lys 
            260                 265                 270         


Pro His Pro Gly Gln Leu Trp Ala Ala Asp Gln Met Ile Ser Leu Leu 
        275                 280                 285             


Ala Gly Ser Gln Leu Val Arg Asp Glu Leu Asp Gly Lys His Asp Trp 
    290                 295                 300                 


Arg Asp Gly Glu Leu Ile Gln Asp Arg Tyr Ser Leu Arg Cys Leu Pro 
305                 310                 315                 320 


Gln Tyr Leu Gly Pro Ile Val Asp Gly Ile Ser Gln Ile Ala Lys Gln 
                325                 330                 335     


Ile Glu Ile Glu Ile Asn Ser Val Thr Asp Asn Pro Leu Ile Asp Val 
            340                 345                 350         


Asp Asn Gln Ala Ser Tyr Tyr Gly Gly Asn Phe Leu Gly Gln Tyr Val 
        355                 360                 365             


Gly Met Gly Met Asp His Leu Arg Tyr Tyr Ile Gly Leu Leu Ala Lys 
    370                 375                 380                 


His Leu Asp Val Gln Ile Ala Leu Leu Asn Ser Pro Glu Phe Ser Asn 
385                 390                 395                 400 


Gly Leu Pro Pro Ser Leu Val Gly Asn Arg Glu Arg Lys Val Asn Met 
                405                 410                 415     


Gly Leu Lys Gly Thr Gln Ile Val Gly Asn Ser Ile Met Pro Leu Leu 
            420                 425                 430         


Thr Phe Tyr Gly Asn Ser Ile Ala Asp Arg Phe Pro Thr His Ala Glu 
        435                 440                 445             


Gln Phe Asn Gln Asn Ile Asn Ser Gln Gly Tyr Thr Ser Ala Thr Leu 
    450                 455                 460                 


Ala Arg Arg Ser Val Asp Ile Phe Gln Asn Tyr Val Ala Ile Ala Leu 
465                 470                 475                 480 


Met Phe Gly Val Gln Ala Val Asp Leu Arg Thr Tyr Lys Lys Thr Gly 
                485                 490                 495     


His Tyr Asp Ala Arg Ala Cys Leu Ser Pro Ala Thr Glu Arg Leu Tyr 
            500                 505                 510         


Ser Ala Val Arg His Val Val Gly Gln Lys Pro Ser Ser Asp Arg Pro 
        515                 520                 525             


Tyr Ile Trp Asn Asp Asn Glu Gln Gly Leu Asp Glu His Ile Ala Arg 
    530                 535                 540                 


Ile Ser Ala Asp Ile Ala Ala Gly Gly Val Ile Val Gln Ala Val Gln 
545                 550                 555                 560 


Asp Ile Leu Pro Cys Gly His 
                565         


<210>  5
<211>  1701
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  SEQ ID NO: 5 - PAL-128 DNA sequence - Variant of Phenylalanine Ammonia Lyase from Anabaena variabilis



<400>  5
atgaaacctt tgccacagga tcagagcaaa accagcagcc agcagtttag ctttaccggc       60

aatagcagcg caaatgtgat tattggtaat cagaaactga ccatcaatga tgttgtacgt      120

gttgcccgta atggcacccc ggttagcctg accaataata cggatattct gcagggtatt      180

caggccagct gtgattatat caataatgca gttgaaagcg gtgaacacat ttatggtgtg      240

acctcgggcc caggtggtat ggcaaatgtt gtaattagcc gtgaacaggc cagcgaactg      300

cagatgaatg cgatttgggc ccttaaaacc ggcgcaggta ataaactgcc gctggcagat      360

gttcgtgcag caatgctgct gcgtgcaaat agccacatgc gtggtgcaag cggtattcgt      420

ctggaactga ttaaacgcat ggaaatcttt ctgaatgccg gtgttacccc gtatgtttat      480

gaatttggta gcattggtgc cagcggtgat ctggtcccgg gatcgtatat taccggtagc      540

ctgattggtc tggacccgag ctttaaagtt gattttaatg gcaaagaaat ggacgcaccg      600

accgcactgc gtcagctgaa tctgagtccg ctgaccctgc tgccgaagga aggctgcagc      660

atggtaaatg gcaccagcgt tatgaccggt attgcagcaa attgtgttta tgatacccag      720

attctgaccg caattgcaat gggtgttcat gcactggata ttcaggcact gaatggtaca      780

aatcagagct ttcatccgtt tatccataac agcaaaccgc atccgggtca gctgtgggca      840

gcagatcaga tgattagcct gctggccggt agccagctgg ttcgtgatga actggatggt      900

aaacatgatt cgcgtgatgg cgaactgatt caggatcgtt atagcctgcg ttgtctgccg      960

cagtatctgg gtccgattgt tgatggtatt agccagattg ccaaacaaat cgaaattgag     1020

attaacagcg ttaccgataa cccgctgatt gatgttgata atcaggcaag ctattatggt     1080

ggtaattttc tgggtcagta tgttggtatg ggtatggatc atctgcgcta ttatatcggt     1140

ctgctggcaa aacatctgga tgttcagatt gcactgctga actcaccgga atttagcaat     1200

ggtctgcctc cgagtctggt gggtaataga gaacgtaaag ttaatatggg tctgaaaggc     1260

actcagattg taggtaatag cattatgccg ctgctgacct tttatggtaa tagtattgca     1320

gatcgttttc cgacccatgc cgaacagttt aaccagaata ttaacagcca gggttatgcg     1380

agcgcaaccc tggcacgtcg tagcgttgat atttttcaga attatgttgc cattgccctg     1440

atgtttggtg ttcaggcagt tgatctgcgt acctacaaaa aaaccggtca ttatgatgca     1500

cgtgcatgtc tgtcaccggc aaccgaacgt ctgtatagcg cagttcgtca cgttgttggt     1560

cagaaaccgg cgtcagatcg tccgtatatt tggaatgata atgaacaggg tctggatgaa     1620

catattgcac gtattagtgc agatattgca gccggtggtc gcattgttca ggccgttcag     1680

gacattctgc cgtgtggaca t                                               1701


<210>  6
<211>  567
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  SEQ ID NO: 6 - PAL-128 protein sequence - Variant of Phenylalanine Ammonia Lyase from Anabaena variabilis



<400>  6

Met Lys Pro Leu Pro Gln Asp Gln Ser Lys Thr Ser Ser Gln Gln Phe 
1               5                   10                  15      


Ser Phe Thr Gly Asn Ser Ser Ala Asn Val Ile Ile Gly Asn Gln Lys 
            20                  25                  30          


Leu Thr Ile Asn Asp Val Val Arg Val Ala Arg Asn Gly Thr Pro Val 
        35                  40                  45              


Ser Leu Thr Asn Asn Thr Asp Ile Leu Gln Gly Ile Gln Ala Ser Cys 
    50                  55                  60                  


Asp Tyr Ile Asn Asn Ala Val Glu Ser Gly Glu His Ile Tyr Gly Val 
65                  70                  75                  80  


Thr Ser Gly Pro Gly Gly Met Ala Asn Val Val Ile Ser Arg Glu Gln 
                85                  90                  95      


Ala Ser Glu Leu Gln Met Asn Ala Ile Trp Ala Leu Lys Thr Gly Ala 
            100                 105                 110         


Gly Asn Lys Leu Pro Leu Ala Asp Val Arg Ala Ala Met Leu Leu Arg 
        115                 120                 125             


Ala Asn Ser His Met Arg Gly Ala Ser Gly Ile Arg Leu Glu Leu Ile 
    130                 135                 140                 


Lys Arg Met Glu Ile Phe Leu Asn Ala Gly Val Thr Pro Tyr Val Tyr 
145                 150                 155                 160 


Glu Phe Gly Ser Ile Gly Ala Ser Gly Asp Leu Val Pro Gly Ser Tyr 
                165                 170                 175     


Ile Thr Gly Ser Leu Ile Gly Leu Asp Pro Ser Phe Lys Val Asp Phe 
            180                 185                 190         


Asn Gly Lys Glu Met Asp Ala Pro Thr Ala Leu Arg Gln Leu Asn Leu 
        195                 200                 205             


Ser Pro Leu Thr Leu Leu Pro Lys Glu Gly Cys Ser Met Val Asn Gly 
    210                 215                 220                 


Thr Ser Val Met Thr Gly Ile Ala Ala Asn Cys Val Tyr Asp Thr Gln 
225                 230                 235                 240 


Ile Leu Thr Ala Ile Ala Met Gly Val His Ala Leu Asp Ile Gln Ala 
                245                 250                 255     


Leu Asn Gly Thr Asn Gln Ser Phe His Pro Phe Ile His Asn Ser Lys 
            260                 265                 270         


Pro His Pro Gly Gln Leu Trp Ala Ala Asp Gln Met Ile Ser Leu Leu 
        275                 280                 285             


Ala Gly Ser Gln Leu Val Arg Asp Glu Leu Asp Gly Lys His Asp Ser 
    290                 295                 300                 


Arg Asp Gly Glu Leu Ile Gln Asp Arg Tyr Ser Leu Arg Cys Leu Pro 
305                 310                 315                 320 


Gln Tyr Leu Gly Pro Ile Val Asp Gly Ile Ser Gln Ile Ala Lys Gln 
                325                 330                 335     


Ile Glu Ile Glu Ile Asn Ser Val Thr Asp Asn Pro Leu Ile Asp Val 
            340                 345                 350         


Asp Asn Gln Ala Ser Tyr Tyr Gly Gly Asn Phe Leu Gly Gln Tyr Val 
        355                 360                 365             


Gly Met Gly Met Asp His Leu Arg Tyr Tyr Ile Gly Leu Leu Ala Lys 
    370                 375                 380                 


His Leu Asp Val Gln Ile Ala Leu Leu Asn Ser Pro Glu Phe Ser Asn 
385                 390                 395                 400 


Gly Leu Pro Pro Ser Leu Val Gly Asn Arg Glu Arg Lys Val Asn Met 
                405                 410                 415     


Gly Leu Lys Gly Thr Gln Ile Val Gly Asn Ser Ile Met Pro Leu Leu 
            420                 425                 430         


Thr Phe Tyr Gly Asn Ser Ile Ala Asp Arg Phe Pro Thr His Ala Glu 
        435                 440                 445             


Gln Phe Asn Gln Asn Ile Asn Ser Gln Gly Tyr Ala Ser Ala Thr Leu 
    450                 455                 460                 


Ala Arg Arg Ser Val Asp Ile Phe Gln Asn Tyr Val Ala Ile Ala Leu 
465                 470                 475                 480 


Met Phe Gly Val Gln Ala Val Asp Leu Arg Thr Tyr Lys Lys Thr Gly 
                485                 490                 495     


His Tyr Asp Ala Arg Ala Cys Leu Ser Pro Ala Thr Glu Arg Leu Tyr 
            500                 505                 510         


Ser Ala Val Arg His Val Val Gly Gln Lys Pro Ala Ser Asp Arg Pro 
        515                 520                 525             


Tyr Ile Trp Asn Asp Asn Glu Gln Gly Leu Asp Glu His Ile Ala Arg 
    530                 535                 540                 


Ile Ser Ala Asp Ile Ala Ala Gly Gly Arg Ile Val Gln Ala Val Gln 
545                 550                 555                 560 


Asp Ile Leu Pro Cys Gly His 
                565         


<210>  7
<211>  1701
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  SEQ ID NO: 7 - PAL-129 DNA sequence - Variant of Phenylalanine Ammonia Lyase from Anabaena variabilis



<400>  7
atgaaacctt tgccacagga tcagagcaaa accagcagcc agcagtttag ctttaccggc       60

aatagcagcg caaacgtgat tattggtaat cagaaactga ccatcaatga tgttgtacgt      120

gttgcccgta atggcacccc ggttagcctg accaataata cggatattct gcagggtatt      180

caggccagct gtgattatat caataatgca gttgaaagcg gtgaacacat ttatggtgtg      240

acctcgccgc caggtggtat ggcaaatgtt gtaattagcc gtgaacaggc cagcgaactg      300

cagatgaatg cgatttgggc ccttaaaacc ggcgcaggta ataaactgcc gctggcagat      360

gttcgtgcag caatgctgct gcgtgcaaat agccacatgc gtggtgcaag cggtattcgt      420

ctggaactga ttaaacgcat ggaaatcttt ctgaatgccg gtgttacccc gtatgtttat      480

gaatttggta gcattggtgc cagcggtgat ctggtcccgg gatcgtatat taccggtagc      540

ctgattggtc tggacccgag ctttaaagtt gattttaatg gcaaagaaat ggacgcaccg      600

accgcactgc gtcagctgaa cctggaaccg ctgaccctgc tgccgaagga aggctgcgcg      660

atggtaaatg gcaccagcgt tatgaccggt attgcagcaa attgtgttta tgatacccag      720

attctgaccg caattgcaat gggtgttcat gcactggata ttcaggcact gaatggtaca      780

aatcagagct ttcatccgtt tatccataac agcaaaccgc atccgggtca gctgtgggca      840

gcagatcaga tgattagcct gctggccggt agccagctgg ttcgtgatga actggatggt      900

aaacatgatt cgcgtgatgg cgaactgatt caggatcgtt atagcctgcg ttgtctgccg      960

cagtatctgg gtccgattgt tgatggtatt agccagattg ccaaacaaat cgaaattgag     1020

attaacagcg ttaccgataa cccgctgatt gatgttgata atcaggcaag ctattatggt     1080

ggtaattttc tgggtcagta tgttggtatg ggtatggatc atctgcgcta ttatatcggt     1140

ctgctggcaa aacatctgga tgttcagatt gcactgctga attcaccgga atttagcaat     1200

ggtctgcctc cgagtctggt gggtaatatg gaacgtaaag ttaatatggg tctgaaaggc     1260

actcagattg taggtaatag cattatgccg ctgctgacct tttatggtaa tagtattgca     1320

gatcgttttc cgacccatgc cgaacagttt aaccagaata ttaacagcca gggttatgcg     1380

agcgcaaccc tggcacgtcg tagcgttgat atttttcaga attatgttgc cattgccctg     1440

atgtttggtg ttcaggcagt tgatctgcgt acctacaaaa aaaccggtca ttatgatgca     1500

cgtgcatgtc tgtcaccggc aaccgaacgt ctgtatagcg cagttcgtga agttgttggt     1560

cagaaaccgg cgtcagatcg tccgtatatt tggaatgata atgaacaggg tctggatgaa     1620

catattgcac gtattagtgc agatattgca gccggtggtc gcattgttca ggccgttcag     1680

gacattctgc cgtgtggaca t                                               1701


<210>  8
<211>  567
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  SEQ ID NO: 8 - PAL-129 protein sequence - Variant of Phenylalanine Ammonia Lyase from Anabaena variabilis



<400>  8

Met Lys Pro Leu Pro Gln Asp Gln Ser Lys Thr Ser Ser Gln Gln Phe 
1               5                   10                  15      


Ser Phe Thr Gly Asn Ser Ser Ala Asn Val Ile Ile Gly Asn Gln Lys 
            20                  25                  30          


Leu Thr Ile Asn Asp Val Val Arg Val Ala Arg Asn Gly Thr Pro Val 
        35                  40                  45              


Ser Leu Thr Asn Asn Thr Asp Ile Leu Gln Gly Ile Gln Ala Ser Cys 
    50                  55                  60                  


Asp Tyr Ile Asn Asn Ala Val Glu Ser Gly Glu His Ile Tyr Gly Val 
65                  70                  75                  80  


Thr Ser Pro Pro Gly Gly Met Ala Asn Val Val Ile Ser Arg Glu Gln 
                85                  90                  95      


Ala Ser Glu Leu Gln Met Asn Ala Ile Trp Ala Leu Lys Thr Gly Ala 
            100                 105                 110         


Gly Asn Lys Leu Pro Leu Ala Asp Val Arg Ala Ala Met Leu Leu Arg 
        115                 120                 125             


Ala Asn Ser His Met Arg Gly Ala Ser Gly Ile Arg Leu Glu Leu Ile 
    130                 135                 140                 


Lys Arg Met Glu Ile Phe Leu Asn Ala Gly Val Thr Pro Tyr Val Tyr 
145                 150                 155                 160 


Glu Phe Gly Ser Ile Gly Ala Ser Gly Asp Leu Val Pro Gly Ser Tyr 
                165                 170                 175     


Ile Thr Gly Ser Leu Ile Gly Leu Asp Pro Ser Phe Lys Val Asp Phe 
            180                 185                 190         


Asn Gly Lys Glu Met Asp Ala Pro Thr Ala Leu Arg Gln Leu Asn Leu 
        195                 200                 205             


Glu Pro Leu Thr Leu Leu Pro Lys Glu Gly Cys Ala Met Val Asn Gly 
    210                 215                 220                 


Thr Ser Val Met Thr Gly Ile Ala Ala Asn Cys Val Tyr Asp Thr Gln 
225                 230                 235                 240 


Ile Leu Thr Ala Ile Ala Met Gly Val His Ala Leu Asp Ile Gln Ala 
                245                 250                 255     


Leu Asn Gly Thr Asn Gln Ser Phe His Pro Phe Ile His Asn Ser Lys 
            260                 265                 270         


Pro His Pro Gly Gln Leu Trp Ala Ala Asp Gln Met Ile Ser Leu Leu 
        275                 280                 285             


Ala Gly Ser Gln Leu Val Arg Asp Glu Leu Asp Gly Lys His Asp Ser 
    290                 295                 300                 


Arg Asp Gly Glu Leu Ile Gln Asp Arg Tyr Ser Leu Arg Cys Leu Pro 
305                 310                 315                 320 


Gln Tyr Leu Gly Pro Ile Val Asp Gly Ile Ser Gln Ile Ala Lys Gln 
                325                 330                 335     


Ile Glu Ile Glu Ile Asn Ser Val Thr Asp Asn Pro Leu Ile Asp Val 
            340                 345                 350         


Asp Asn Gln Ala Ser Tyr Tyr Gly Gly Asn Phe Leu Gly Gln Tyr Val 
        355                 360                 365             


Gly Met Gly Met Asp His Leu Arg Tyr Tyr Ile Gly Leu Leu Ala Lys 
    370                 375                 380                 


His Leu Asp Val Gln Ile Ala Leu Leu Asn Ser Pro Glu Phe Ser Asn 
385                 390                 395                 400 


Gly Leu Pro Pro Ser Leu Val Gly Asn Met Glu Arg Lys Val Asn Met 
                405                 410                 415     


Gly Leu Lys Gly Thr Gln Ile Val Gly Asn Ser Ile Met Pro Leu Leu 
            420                 425                 430         


Thr Phe Tyr Gly Asn Ser Ile Ala Asp Arg Phe Pro Thr His Ala Glu 
        435                 440                 445             


Gln Phe Asn Gln Asn Ile Asn Ser Gln Gly Tyr Ala Ser Ala Thr Leu 
    450                 455                 460                 


Ala Arg Arg Ser Val Asp Ile Phe Gln Asn Tyr Val Ala Ile Ala Leu 
465                 470                 475                 480 


Met Phe Gly Val Gln Ala Val Asp Leu Arg Thr Tyr Lys Lys Thr Gly 
                485                 490                 495     


His Tyr Asp Ala Arg Ala Cys Leu Ser Pro Ala Thr Glu Arg Leu Tyr 
            500                 505                 510         


Ser Ala Val Arg Glu Val Val Gly Gln Lys Pro Ala Ser Asp Arg Pro 
        515                 520                 525             


Tyr Ile Trp Asn Asp Asn Glu Gln Gly Leu Asp Glu His Ile Ala Arg 
    530                 535                 540                 


Ile Ser Ala Asp Ile Ala Ala Gly Gly Arg Ile Val Gln Ala Val Gln 
545                 550                 555                 560 


Asp Ile Leu Pro Cys Gly His 
                565         


<210>  9
<211>  1701
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  SEQ ID NO: 9 - PAL-130 DNA sequence - Variant of Phenylalanine Ammonia Lyase from Anabaena variabilis



<400>  9
atgaaacctt tgccacagga tcagagcaaa accagcagcc agcagtttag ctttaccggc       60

aatagcagcg caaacgtgat tattggtaat cagaaactga ccatcaatga tgttgtacgt      120

gttgcccgta atggcacccc ggttagcctg accaataatc cggatattct gcagggtatt      180

caggccagct gtgattatat caataatgca gttgaaagcg gtgaacacat ttatggtgtg      240

acctcgccgc caggtggtat ggcaaatgtt gtaattagcc gtgaacaggc cagcgaactg      300

cagatgaatg cgatttgggc ccttaaaacc ggcgcaggta ataaactgcc gctggcagat      360

gttcgtgcag caatgctgct gcgtgcaaat agccacatgc gtggtgcaag cggtattcgt      420

ctggaactga ttaaacgcat ggaaatcttt ctgaatgccg gtgttacccc gtatgtttat      480

gaatttggta gcattggtgc cagcggtgat ctggtcccgg gatcgtatat taccggtagc      540

ctgattggtc tggacccgag ctttaaagtt gattttaatg gcaaagaaat ggacgcaccg      600

accgcactgc gtcagctgaa cctggagccg ctgaccctgc tgccgaagga aggctgcgcg      660

atggtaaatg gcaccagcgt tatgaccggt attgcagcaa attgtgttta tgatacccag      720

attctgaccg caattgcaat gggtgttcat gcactggata ttcaggcact gaatggtaca      780

aatcagagct ttcatccgtt tatccataac agcaaaccgc atccgggtca gctgtgggca      840

gcagatcaga tgattagcct gctggccggt agccagctgg ttcgtgatga actggatggt      900

aaacatgatt cgcgtgatgg cgaactgatt caggatcgtt atagcctgcg ttgtctgccg      960

cagtatctgg gtccgattgt tgatggtatt agccagattg ccaaacaaat cgaaattgag     1020

attaacagcg ttaccgataa cccgctgatt gatgttgata atcaggcaag ctattatggt     1080

ggtaattttc tgggtcagta tgttggtatg ggtatggatc atctgcgcta ttatatcggt     1140

ctgctggcaa aacatctgga tgttcagatt gcactgctga attcaccgga atttagcaat     1200

ggtctgcctc cgagtctggt gggtaatatg gaacgtaaag ttaatatggg tctgaaaggc     1260

actcagattg ctggtaatag cattatgccg ctgctgacct tttatggtaa tagtattgca     1320

gatcgttttc cgacccatgc cgaacagttt aaccagaata ttaacagcca gggttatgcg     1380

agcgcaaccc tggcacgtcg tagcgttgat atttttcaga attatgttgc cattgccctg     1440

atgtttggtg ttcaggcagt tgatctgcgt acctacaaaa aaaccggtca ttatgatgca     1500

cgtgcatgtc tgtcaccggc aaccgaacgt ctgtatagcg cagttcgtga agttgttggc     1560

cagaaaccgg cgtcagatcg tccgtatatt tggaatgata atgaacaggg tctggatgaa     1620

catattgcac gtattagtgc agatattgca gccggtggtc gcattgttca ggccgttcag     1680

gacattctgc cgtgtggaca t                                               1701


<210>  10
<211>  567
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  SEQ ID NO: 10 - PAL-130 protein sequence - Variant of Phenylalanine Ammonia Lyase from Anabaena variabilis



<400>  10

Met Lys Pro Leu Pro Gln Asp Gln Ser Lys Thr Ser Ser Gln Gln Phe 
1               5                   10                  15      


Ser Phe Thr Gly Asn Ser Ser Ala Asn Val Ile Ile Gly Asn Gln Lys 
            20                  25                  30          


Leu Thr Ile Asn Asp Val Val Arg Val Ala Arg Asn Gly Thr Pro Val 
        35                  40                  45              


Ser Leu Thr Asn Asn Pro Asp Ile Leu Gln Gly Ile Gln Ala Ser Cys 
    50                  55                  60                  


Asp Tyr Ile Asn Asn Ala Val Glu Ser Gly Glu His Ile Tyr Gly Val 
65                  70                  75                  80  


Thr Ser Pro Pro Gly Gly Met Ala Asn Val Val Ile Ser Arg Glu Gln 
                85                  90                  95      


Ala Ser Glu Leu Gln Met Asn Ala Ile Trp Ala Leu Lys Thr Gly Ala 
            100                 105                 110         


Gly Asn Lys Leu Pro Leu Ala Asp Val Arg Ala Ala Met Leu Leu Arg 
        115                 120                 125             


Ala Asn Ser His Met Arg Gly Ala Ser Gly Ile Arg Leu Glu Leu Ile 
    130                 135                 140                 


Lys Arg Met Glu Ile Phe Leu Asn Ala Gly Val Thr Pro Tyr Val Tyr 
145                 150                 155                 160 


Glu Phe Gly Ser Ile Gly Ala Ser Gly Asp Leu Val Pro Gly Ser Tyr 
                165                 170                 175     


Ile Thr Gly Ser Leu Ile Gly Leu Asp Pro Ser Phe Lys Val Asp Phe 
            180                 185                 190         


Asn Gly Lys Glu Met Asp Ala Pro Thr Ala Leu Arg Gln Leu Asn Leu 
        195                 200                 205             


Glu Pro Leu Thr Leu Leu Pro Lys Glu Gly Cys Ala Met Val Asn Gly 
    210                 215                 220                 


Thr Ser Val Met Thr Gly Ile Ala Ala Asn Cys Val Tyr Asp Thr Gln 
225                 230                 235                 240 


Ile Leu Thr Ala Ile Ala Met Gly Val His Ala Leu Asp Ile Gln Ala 
                245                 250                 255     


Leu Asn Gly Thr Asn Gln Ser Phe His Pro Phe Ile His Asn Ser Lys 
            260                 265                 270         


Pro His Pro Gly Gln Leu Trp Ala Ala Asp Gln Met Ile Ser Leu Leu 
        275                 280                 285             


Ala Gly Ser Gln Leu Val Arg Asp Glu Leu Asp Gly Lys His Asp Ser 
    290                 295                 300                 


Arg Asp Gly Glu Leu Ile Gln Asp Arg Tyr Ser Leu Arg Cys Leu Pro 
305                 310                 315                 320 


Gln Tyr Leu Gly Pro Ile Val Asp Gly Ile Ser Gln Ile Ala Lys Gln 
                325                 330                 335     


Ile Glu Ile Glu Ile Asn Ser Val Thr Asp Asn Pro Leu Ile Asp Val 
            340                 345                 350         


Asp Asn Gln Ala Ser Tyr Tyr Gly Gly Asn Phe Leu Gly Gln Tyr Val 
        355                 360                 365             


Gly Met Gly Met Asp His Leu Arg Tyr Tyr Ile Gly Leu Leu Ala Lys 
    370                 375                 380                 


His Leu Asp Val Gln Ile Ala Leu Leu Asn Ser Pro Glu Phe Ser Asn 
385                 390                 395                 400 


Gly Leu Pro Pro Ser Leu Val Gly Asn Met Glu Arg Lys Val Asn Met 
                405                 410                 415     


Gly Leu Lys Gly Thr Gln Ile Ala Gly Asn Ser Ile Met Pro Leu Leu 
            420                 425                 430         


Thr Phe Tyr Gly Asn Ser Ile Ala Asp Arg Phe Pro Thr His Ala Glu 
        435                 440                 445             


Gln Phe Asn Gln Asn Ile Asn Ser Gln Gly Tyr Ala Ser Ala Thr Leu 
    450                 455                 460                 


Ala Arg Arg Ser Val Asp Ile Phe Gln Asn Tyr Val Ala Ile Ala Leu 
465                 470                 475                 480 


Met Phe Gly Val Gln Ala Val Asp Leu Arg Thr Tyr Lys Lys Thr Gly 
                485                 490                 495     


His Tyr Asp Ala Arg Ala Cys Leu Ser Pro Ala Thr Glu Arg Leu Tyr 
            500                 505                 510         


Ser Ala Val Arg Glu Val Val Gly Gln Lys Pro Ala Ser Asp Arg Pro 
        515                 520                 525             


Tyr Ile Trp Asn Asp Asn Glu Gln Gly Leu Asp Glu His Ile Ala Arg 
    530                 535                 540                 


Ile Ser Ala Asp Ile Ala Ala Gly Gly Arg Ile Val Gln Ala Val Gln 
545                 550                 555                 560 


Asp Ile Leu Pro Cys Gly His 
                565         

<210> 11
<211> 1701

<212> DNA

<213> Artificial Sequence

<220>

<223> SEQ ID NO: 11 - PAL-131 DNA sequence - Variant of Phenylalanine Ammonia Lyase from Anabaena variabilis


<400> 11

atgaaacctt tgccacagga tcagagcaaa accagcagcc agcagtttag ctttaccggc 60

aatagcagcg caaacgtgat tattggtaat cagaaactga ccatcaatga tgttgtatgc 120

gttgcccgta atggcacccc ggttagcctg accaataatc cggatattct gcagggtatt 180

caggccagct gtgattttat caataatgca gttgaaagcg gtgaacacat ttatggtgtg 240

acctcgccgc caggtggtat ggcaaatgtt gtaattagcc gtgaacaggc cagcgaactg 300

cagatgaatg cgatttgggc ccttaaaacc ggcgcaggta ataaactgcc gctggcagat 360

gttcgtgcag caatgctgct gcgtgcaaat agccacatgc gtggtgcaag cggtattcgt 420
ctggaactga ttaaacgcat ggaaatcttt ctgaatgccg gtgttacccc gtatgtttat 480

gaatttggta gcattggtgc cagcggtgat ctggtcccgg gatcgtatat taccggtagc 540

ctgattggtc tggacccgag ctttaaagtt gattttaatg gcaaagaaat ggacgcaccg 600

accgcactgc gtcagctgaa cctggagccg ctgaccctgc tgccgaagga aggctgcgcg 660

atggtaaatg gcaccagcgt tatgaccggt attgcagcaa attgtgttta tgatacccag 720

attctgaccg cgattgcaat gggtgttcat gcactggata ttcaggcact gaatggtaca 780

aatcagagct ttcatccgtt tatccataac agcaaaccgc atccgggtca gctgtgggca 840

gcagatcaga tgattagcct gctggccggt agccagctgg ttcgtgatga actggatggt 900

aaacatgatt cgcgtgatgg cgaactgatt caggatcgtt atagcctgcg ttgtctgccg 960

cagtatctgg gtccgattgt tgatggtatt agccagattg ccaaacaaat cgaaattgag 1020

attaacagcg ttaccgataa cccgctgatt gatgttgata atcaggcaag ctattatggt 1080

ggtaattttc tgggtcagta tgttggtatg ggtatggatc atctgcgcta ttatatcggt 1140

ctgctggcaa aacatctgga tgttcagatt gcactgctga attcaccgga atttagcaat 1200

ggtctgcctc cgagtctggt gggtaataag gaacgtaaag ttaatatggg tctgaaaggc 1260

actcagattg caggtaatag cattatgccg ctgctgacct tttatggtaa tagtattgca 1320

gatcgttttc cgacccatgc cgaacagttt aaccagaata ttaacagcca gggttatgcg 1380

agcgcaaccc tggcacgtcg tagcgttgat atttttcagg agtatgttgc cattgccctg 1440

atgtttggtg ttcaggcagt tgatctgcgt acctacaaaa aaaccggtca ttatgatgca 1500

cgtgcatgtc tgtcaccggc aaccgaacgt ctgtatagcg cagttcgtga agttgttggc 1560

cagaaaccgg cgtcagatcg tccgtatatt tggaatgata atgaacaggg tctggatgaa 1620

catattgcac gtattagtgc agatattgca gccggtggtc gcattgttca ggccgttcag 1680

gacattctgc cgtgtggaca t                                           1701



<210> 12

<211> 567

<212> PRT

<213> Artificial Sequence
 

<220>

<223> SEQ ID NO: 12 - PAL-131 protein sequence - Variant of Phenylalanine Ammonia Lyase from Anabaena variabilis


<400> 12

Met Lys Pro Leu Pro Gln Asp Gln Ser Lys Thr Ser Ser Gln Gln Phe
 
1               5                  10                  15      

Ser Phe Thr Gly Asn Ser Ser Ala Asn Val Ile Ile Gly Asn Gln Lys 

            20                  25                  30          

Leu Thr Ile Asn Asp Val Val Cys Val Ala Arg Asn Gly Thr Pro Val
 
       35                  40                  45              

Ser Leu Thr Asn Asn Pro Asp Ile Leu Gln Gly Ile Gln Ala Ser Cys
 
   50                  55                  60                  

Asp Phe Ile Asn Asn Ala Val Glu Ser Gly Glu His Ile Tyr Gly Val 

65                  70                  75                  80
Thr Ser Pro Pro Gly Gly Met Ala Asn Val Val Ile Ser Arg Glu Gln
 
               85                  90                  95

Ala Ser Glu Leu Gln Met Asn Ala Ile Trp Ala Leu Lys Thr Gly Ala
 
           100                 105                 110         

Gly Asn Lys Leu Pro Leu Ala Asp Val Arg Ala Ala Met Leu Leu Arg
 
       115                 120                 125             

Ala Asn Ser His Met Arg Gly Ala Ser Gly Ile Arg Leu Glu Leu Ile
 
   130                 135                 140                 

Lys Arg Met Glu Ile Phe Leu Asn Ala Gly Val Thr Pro Tyr Val Tyr

145                 150                 155                 160

Glu Phe Gly Ser Ile Gly Ala Ser Gly Asp Leu Val Pro Gly Ser Tyr
 
               165                 170                 175     

Ile Thr Gly Ser Leu Ile Gly Leu Asp Pro Ser Phe Lys Val Asp Phe
 
           180                 185                 190         

Asn Gly Lys Glu Met Asp Ala Pro Thr Ala Leu Arg Gln Leu Asn Leu
 
       195                 200                 205             

Glu Pro Leu Thr Leu Leu Pro Lys Glu Gly Cys Ala Met Val Asn Gly
 
   210                 215                 220                 

Thr Ser Val Met Thr Gly Ile Ala Ala Asn Cys Val Tyr Asp Thr Gln
225                 230                 235                 240 

Ile Leu Thr Ala Ile Ala Met Gly Val His Ala Leu Asp Ile Gln Ala
 
               245                 250                 255     

Leu Asn Gly Thr Asn Gln Ser Phe His Pro Phe Ile His Asn Ser Lys
 
           260                 265                 270         

Pro His Pro Gly Gln Leu Trp Ala Ala Asp Gln Met Ile Ser Leu Leu
 
       275                 280                 285             
Ala Gly Ser Gln Leu Val Arg Asp Glu Leu Asp Gly Lys His Asp Ser
 
   290                 295                 300                 

Arg Asp Gly Glu Leu Ile Gln Asp Arg Tyr Ser Leu Arg Cys Leu Pro

305                 310                 315                 320

Gln Tyr Leu Gly Pro Ile Val Asp Gly Ile Ser Gln Ile Ala Lys Gln
 
               325                 330                 335     

Ile Glu Ile Glu Ile Asn Ser Val Thr Asp Asn Pro Leu Ile Asp Val
 
           340                 345                 350        

Asp Asn Gln Ala Ser Tyr Tyr Gly Gly Asn Phe Leu Gly Gln Tyr Val
 
       355                 360                 365             

Gly Met Gly Met Asp His Leu Arg Tyr Tyr Ile Gly Leu Leu Ala Lys
 
   370                 375                 380                 

His Leu Asp Val Gln Ile Ala Leu Leu Asn Ser Pro Glu Phe Ser Asn

385                 390                 395                 400

Gly Leu Pro Pro Ser Leu Val Gly Asn Lys Glu Arg Lys Val Asn Met
 
               405                 410                 415     

Gly Leu Lys Gly Thr Gln Ile Ala Gly Asn Ser Ile Met Pro Leu Leu
 
           420                 425                 430         

Thr Phe Tyr Gly Asn Ser Ile Ala Asp Arg Phe Pro Thr His Ala Glu
 
       435                 440                 445             

Gln Phe Asn Gln Asn Ile Asn Ser Gln Gly Tyr Ala Ser Ala Thr Leu
 
   450                 455                 460                 

Ala Arg Arg Ser Val Asp Ile Phe Gln Glu Tyr Val Ala Ile Ala Leu
465                 470                 475                 480 

Met Phe Gly Val Gln Ala Val Asp Leu Arg Thr Tyr Lys Lys Thr Gly
 
               485                 490                 495     

His Tyr Asp Ala Arg Ala Cys Leu Ser Pro Ala Thr Glu Arg Leu Tyr
 
           500                 505                 510         

Ser Ala Val Arg Glu Val Val Gly Gln Lys Pro Ala Ser Asp Arg Pro
 
       515                 520                 525             

Tyr Ile Trp Asn Asp Asn Glu Gln Gly Leu Asp Glu His Ile Ala Arg
 
   530                 535                 540                 

Ile Ser Ala Asp Ile Ala Ala Gly Gly Arg Ile Val Gln Ala Val Gln
545                 550                 555                 560
 
Asp Ile Leu Pro Cys Gly His                                     
                
                 565                                             

 
