                         SEQUENCE LISTING

<110>  BIOMARIN PHARMACEUTICAL INC.
 
<120>  COMPOSITIONS OF PROKARYOTIC PHENYLALANINE AMMONIA-LYASE AND 
       METHODS OF TREATING ADOLESCENT SUBJECTS

<130>  11808-479-228

<140>
<141>

<150>  US 63/190,567
<151>  2021-05-19

<160>  4     

<170>  PatentIn version 3.5

<210>  1
<211>  567
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anabaena variabilis (Av) PAL wild type

<400>  1

Met Lys Thr Leu Ser Gln Ala 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 Ala 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 Pro Ile Tyr Gly Val 
65                  70                  75                  80  


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


Ala Ser Glu Leu Gln Thr Asn Leu Val Trp Phe 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 Leu 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 Leu Ala Met Met 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 Asn Ser Gln Leu Val Arg Asp Glu Leu Asp Gly Lys His Asp Tyr 
    290                 295                 300                 


Arg Asp His 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 His 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 Ala Ser Pro Glu Phe Ser Asn 
385                 390                 395                 400 


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


Gly Leu Lys Gly Leu Gln Ile Cys 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 Thr 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 Leu His 
                565         


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

<220>
<223>  Anabaena variabilis (Av) PAL variant AvPAL_C503S

<400>  2

Met Lys Thr Leu Ser Gln Ala 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 Ala 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 Pro Ile Tyr Gly Val 
65                  70                  75                  80  


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


Ala Ser Glu Leu Gln Thr Asn Leu Val Trp Phe 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 Leu 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 Leu Ala Met Met 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 Asn Ser Gln Leu Val Arg Asp Glu Leu Asp Gly Lys His Asp Tyr 
    290                 295                 300                 


Arg Asp His 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 His 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 Ala Ser Pro Glu Phe Ser Asn 
385                 390                 395                 400 


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


Gly Leu Lys Gly Leu Gln Ile Cys 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 Ser Leu Ser Pro Ala Thr Glu Arg Leu Tyr 
            500                 505                 510         


Ser Ala Val Arg His Val Val Gly Gln Lys Pro Thr 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 Leu His 
                565         


<210>  3
<211>  567
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anabaena variabilis (Av) PAL variant AvPAL_C565S

<400>  3

Met Lys Thr Leu Ser Gln Ala 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 Ala 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 Pro Ile Tyr Gly Val 
65                  70                  75                  80  


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


Ala Ser Glu Leu Gln Thr Asn Leu Val Trp Phe 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 Leu 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 Leu Ala Met Met 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 Asn Ser Gln Leu Val Arg Asp Glu Leu Asp Gly Lys His Asp Tyr 
    290                 295                 300                 


Arg Asp His 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 His 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 Ala Ser Pro Glu Phe Ser Asn 
385                 390                 395                 400 


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


Gly Leu Lys Gly Leu Gln Ile Cys 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 Thr 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 Ser Leu His 
                565         


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

<220>
<223>  Anabaena variabilis (Av) PAL variant AvPAL_ C565SC503S

<400>  4

Met Lys Thr Leu Ser Gln Ala 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 Ala 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 Pro Ile Tyr Gly Val 
65                  70                  75                  80  


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


Ala Ser Glu Leu Gln Thr Asn Leu Val Trp Phe 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 Leu 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 Leu Ala Met Met 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 Asn Ser Gln Leu Val Arg Asp Glu Leu Asp Gly Lys His Asp Tyr 
    290                 295                 300                 


Arg Asp His 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 His 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 Ala Ser Pro Glu Phe Ser Asn 
385                 390                 395                 400 


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


Gly Leu Lys Gly Leu Gln Ile Cys 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 Ser Leu Ser Pro Ala Thr Glu Arg Leu Tyr 
            500                 505                 510         


Ser Ala Val Arg His Val Val Gly Gln Lys Pro Thr 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 Ser Leu His 
                565         


