                         SEQUENCE LISTING

<110>  The General Hospital Corporation
 
<120>  Extracellular Redox Enzyme System to Alleviate Disease

<130>  29539-0295WO1

<150>  US 62/594,323
<151>  2017-12-04

<150>  US 62/630,093
<151>  2018-02-13

<160>  9     

<170>  PatentIn version 3.5

<210>  1
<211>  1199
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  engineered LOXCAT fusion polypeptide

<400>  1

Met His His His His His His Ser Ser Gly Leu Val Pro Arg Gly Ser 
1               5                   10                  15      


Gly Met Lys Glu Thr Ala Ala Ala Lys Phe Glu Arg Gln His Met Asp 
            20                  25                  30          


Ser Pro Asp Leu Gly Thr Asp Asp Asp Asp Lys Ala Met Ala Asp Ile 
        35                  40                  45              


Gly Ser Glu Phe Glu Leu Ser Gln His Asn Glu Lys Asn Pro His Gln 
    50                  55                  60                  


His Gln Ser Pro Leu His Asp Ser Ser Glu Ala Lys Pro Gly Met Asp 
65                  70                  75                  80  


Ser Leu Ala Pro Glu Asp Gly Ser His Arg Pro Ala Ala Glu Pro Thr 
                85                  90                  95      


Pro Pro Gly Ala Gln Pro Thr Ala Pro Gly Ser Leu Lys Ala Pro Asp 
            100                 105                 110         


Thr Arg Asn Glu Lys Leu Asn Ser Leu Glu Asp Val Arg Lys Gly Ser 
        115                 120                 125             


Glu Asn Tyr Ala Leu Thr Thr Asn Gln Gly Val Arg Ile Ala Asp Asp 
    130                 135                 140                 


Gln Asn Ser Leu Arg Ala Gly Ser Arg Gly Pro Thr Leu Leu Glu Asp 
145                 150                 155                 160 


Phe Ile Leu Arg Glu Lys Ile Thr His Phe Asp His Glu Arg Ile Pro 
                165                 170                 175     


Glu Arg Ile Val His Ala Arg Gly Ser Ala Ala His Gly Tyr Phe Gln 
            180                 185                 190         


Pro Tyr Lys Ser Leu Ser Asp Ile Thr Lys Ala Asp Phe Leu Ser Asp 
        195                 200                 205             


Pro Asn Lys Ile Thr Pro Val Phe Val Arg Phe Ser Thr Val Gln Gly 
    210                 215                 220                 


Gly Ala Gly Ser Ala Asp Thr Val Arg Asp Ile Arg Gly Phe Ala Thr 
225                 230                 235                 240 


Lys Phe Tyr Thr Glu Glu Gly Ile Phe Asp Leu Val Gly Asn Asn Thr 
                245                 250                 255     


Pro Ile Phe Phe Ile Gln Asp Ala His Lys Phe Pro Asp Phe Val His 
            260                 265                 270         


Ala Val Lys Pro Glu Pro His Trp Ala Ile Pro Gln Gly Gln Ser Ala 
        275                 280                 285             


His Asp Thr Phe Trp Asp Tyr Val Ser Leu Gln Pro Glu Thr Leu His 
    290                 295                 300                 


Asn Val Met Trp Ala Met Ser Asp Arg Gly Ile Pro Arg Ser Tyr Arg 
305                 310                 315                 320 


Thr Met Glu Gly Phe Gly Ile His Thr Phe Arg Leu Ile Asn Ala Glu 
                325                 330                 335     


Gly Lys Ala Thr Phe Val Arg Phe His Trp Lys Pro Leu Ala Gly Lys 
            340                 345                 350         


Ala Ser Leu Val Trp Asp Glu Ala Gln Lys Leu Thr Gly Arg Asp Pro 
        355                 360                 365             


Asp Phe His Arg Arg Glu Leu Trp Glu Ala Ile Glu Ala Gly Asp Phe 
    370                 375                 380                 


Pro Glu Tyr Glu Leu Gly Phe Gln Leu Ile Pro Glu Glu Asp Glu Phe 
385                 390                 395                 400 


Lys Phe Asp Phe Asp Leu Leu Asp Pro Thr Lys Leu Ile Pro Glu Glu 
                405                 410                 415     


Leu Val Pro Val Gln Arg Val Gly Lys Met Val Leu Asn Arg Asn Pro 
            420                 425                 430         


Asp Asn Phe Phe Ala Glu Asn Glu Gln Ala Ala Phe His Pro Gly His 
        435                 440                 445             


Ile Val Pro Gly Leu Asp Phe Thr Asn Asp Pro Leu Leu Gln Gly Arg 
    450                 455                 460                 


Leu Phe Ser Tyr Thr Asp Thr Gln Ile Ser Arg Leu Gly Gly Pro Asn 
465                 470                 475                 480 


Phe His Glu Ile Pro Ile Asn Arg Pro Thr Cys Pro Tyr His Asn Phe 
                485                 490                 495     


Gln Arg Asp Gly Met His Arg Met Gly Ile Asp Thr Asn Pro Ala Asn 
            500                 505                 510         


Tyr Glu Pro Asn Ser Ile Asn Asp Asn Trp Pro Arg Glu Thr Pro Pro 
        515                 520                 525             


Gly Pro Lys Arg Gly Gly Phe Glu Ser Tyr Gln Glu Arg Val Glu Gly 
    530                 535                 540                 


Asn Lys Val Arg Glu Arg Ser Pro Ser Phe Gly Glu Tyr Tyr Ser His 
545                 550                 555                 560 


Pro Arg Leu Phe Trp Leu Ser Gln Thr Pro Phe Glu Gln Arg His Ile 
                565                 570                 575     


Val Asp Gly Phe Ser Phe Glu Leu Ser Lys Val Val Arg Pro Tyr Ile 
            580                 585                 590         


Arg Glu Arg Val Val Asp Gln Leu Ala His Ile Asp Leu Thr Leu Ala 
        595                 600                 605             


Gln Ala Val Ala Lys Asn Leu Gly Ile Glu Leu Thr Asp Asp Gln Leu 
    610                 615                 620                 


Asn Ile Thr Pro Pro Pro Asp Val Asn Gly Leu Lys Lys Asp Pro Ser 
625                 630                 635                 640 


Leu Ser Leu Tyr Ala Ile Pro Asp Gly Asp Val Lys Gly Arg Val Val 
                645                 650                 655     


Ala Ile Leu Leu Asn Asp Glu Val Arg Ser Ala Asp Leu Leu Ala Ile 
            660                 665                 670         


Leu Lys Ala Leu Lys Ala Lys Gly Val His Ala Lys Leu Leu Tyr Ser 
        675                 680                 685             


Arg Met Gly Glu Val Thr Ala Asp Asp Gly Thr Val Leu Pro Ile Ala 
    690                 695                 700                 


Ala Thr Phe Ala Gly Ala Pro Ser Leu Thr Val Asp Ala Val Ile Val 
705                 710                 715                 720 


Pro Cys Gly Asn Ile Ala Asp Ile Ala Asp Asn Gly Asp Ala Asn Tyr 
                725                 730                 735     


Tyr Leu Met Glu Ala Tyr Lys His Leu Lys Pro Ile Ala Leu Ala Gly 
            740                 745                 750         


Asp Ala Arg Lys Phe Lys Ala Thr Ile Lys Ile Ala Asp Gln Gly Glu 
        755                 760                 765             


Glu Gly Ile Val Glu Ala Asp Ser Ala Asp Gly Ser Phe Met Asp Glu 
    770                 775                 780                 


Leu Leu Thr Leu Met Ala Ala His Arg Val Trp Ser Arg Ile Pro Lys 
785                 790                 795                 800 


Ile Asp Lys Ile Pro Ala Ala Ser Gly Ala Gly Gly Ser Glu Gly Gly 
                805                 810                 815     


Gly Ser Glu Gly Gly Thr Ser Gly Ala Thr Asn Asn Asn Asp Ile Glu 
            820                 825                 830         


Tyr Asn Ala Pro Ser Glu Ile Lys Tyr Ile Asp Val Val Asn Thr Tyr 
        835                 840                 845             


Asp Leu Glu Glu Glu Ala Ser Lys Val Val Pro His Gly Gly Phe Asn 
    850                 855                 860                 


Tyr Ile Ala Gly Ala Ser Gly Asp Glu Trp Thr Lys Arg Ala Asn Asp 
865                 870                 875                 880 


Arg Ala Trp Lys His Lys Leu Leu Tyr Pro Arg Leu Ala Gln Asp Val 
                885                 890                 895     


Glu Ala Pro Asp Thr Ser Thr Glu Ile Leu Gly His Lys Ile Lys Ala 
            900                 905                 910         


Pro Phe Ile Met Ala Pro Ile Ala Ala His Gly Leu Ala His Thr Thr 
        915                 920                 925             


Lys Glu Ala Gly Thr Ala Arg Ala Val Ser Glu Phe Gly Thr Ile Met 
    930                 935                 940                 


Ser Ile Ser Ala Tyr Ser Gly Ala Thr Phe Glu Glu Ile Ser Glu Gly 
945                 950                 955                 960 


Leu Asn Gly Gly Pro Arg Trp Phe Gln Ile Tyr Met Ala Lys Asp Asp 
                965                 970                 975     


Gln Gln Asn Arg Asp Ile Leu Asp Glu Ala Lys Ser Asp Gly Ala Thr 
            980                 985                 990         


Ala Ile Ile Leu Thr Ala Asp Ser  Thr Val Ser Gly Asn  Arg Asp Arg 
        995                 1000                 1005             


Asp Val  Lys Asn Lys Phe Val  Tyr Pro Phe Gly Met  Pro Ile Val 
    1010                 1015                 1020             


Gln Arg  Tyr Leu Arg Gly Thr  Ala Glu Gly Met Ser  Leu Asn Asn 
    1025                 1030                 1035             


Ile Tyr  Gly Ala Ser Lys Gln  Lys Ile Ser Pro Arg  Asp Ile Glu 
    1040                 1045                 1050             


Glu Ile  Ala Gly His Ser Gly  Leu Pro Val Phe Val  Lys Gly Ile 
    1055                 1060                 1065             


Gln His  Pro Glu Asp Ala Asp  Met Ala Ile Lys Arg  Gly Ala Ser 
    1070                 1075                 1080             


Gly Ile  Trp Val Ser Asn His  Gly Ala Arg Gln Leu  Tyr Glu Ala 
    1085                 1090                 1095             


Pro Gly  Ser Phe Asp Thr Leu  Pro Ala Ile Ala Glu  Arg Val Asn 
    1100                 1105                 1110             


Lys Arg  Val Pro Ile Val Phe  Asp Ser Gly Val Arg  Arg Gly Glu 
    1115                 1120                 1125             


His Val  Ala Lys Ala Leu Ala  Ser Gly Ala Asp Val  Val Ala Leu 
    1130                 1135                 1140             


Gly Arg  Pro Val Leu Phe Gly  Leu Ala Leu Gly Gly  Trp Gln Gly 
    1145                 1150                 1155             


Ala Tyr  Ser Val Leu Asp Tyr  Phe Gln Lys Asp Leu  Thr Arg Val 
    1160                 1165                 1170             


Met Gln  Leu Thr Gly Ser Gln  Asn Val Glu Asp Leu  Lys Gly Leu 
    1175                 1180                 1185             


Asp Leu  Phe Asp Asn Pro Tyr  Gly Tyr Glu Tyr 
    1190                 1195                 


<210>  2
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  thrombin cleavage site

<400>  2

Leu Val Pro Arg Gly Ser 
1               5       


<210>  3
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  enterokinase/enteropeptidase cleavage site

<400>  3

Asp Asp Asp Asp Lys 
1               5   


<210>  4
<211>  752
<212>  PRT
<213>  Escherichia coli


<220>
<221>  MISC_FEATURE
<223>  Catalase (HPII)

<400>  4

Ser Gln His Asn Glu Lys Asn Pro His Gln His Gln Ser Pro Leu His 
1               5                   10                  15      


Asp Ser Ser Glu Ala Lys Pro Gly Met Asp Ser Leu Ala Pro Glu Asp 
            20                  25                  30          


Gly Ser His Arg Pro Ala Ala Glu Pro Thr Pro Pro Gly Ala Gln Pro 
        35                  40                  45              


Thr Ala Pro Gly Ser Leu Lys Ala Pro Asp Thr Arg Asn Glu Lys Leu 
    50                  55                  60                  


Asn Ser Leu Glu Asp Val Arg Lys Gly Ser Glu Asn Tyr Ala Leu Thr 
65                  70                  75                  80  


Thr Asn Gln Gly Val Arg Ile Ala Asp Asp Gln Asn Ser Leu Arg Ala 
                85                  90                  95      


Gly Ser Arg Gly Pro Thr Leu Leu Glu Asp Phe Ile Leu Arg Glu Lys 
            100                 105                 110         


Ile Thr His Phe Asp His Glu Arg Ile Pro Glu Arg Ile Val His Ala 
        115                 120                 125             


Arg Gly Ser Ala Ala His Gly Tyr Phe Gln Pro Tyr Lys Ser Leu Ser 
    130                 135                 140                 


Asp Ile Thr Lys Ala Asp Phe Leu Ser Asp Pro Asn Lys Ile Thr Pro 
145                 150                 155                 160 


Val Phe Val Arg Phe Ser Thr Val Gln Gly Gly Ala Gly Ser Ala Asp 
                165                 170                 175     


Thr Val Arg Asp Ile Arg Gly Phe Ala Thr Lys Phe Tyr Thr Glu Glu 
            180                 185                 190         


Gly Ile Phe Asp Leu Val Gly Asn Asn Thr Pro Ile Phe Phe Ile Gln 
        195                 200                 205             


Asp Ala His Lys Phe Pro Asp Phe Val His Ala Val Lys Pro Glu Pro 
    210                 215                 220                 


His Trp Ala Ile Pro Gln Gly Gln Ser Ala His Asp Thr Phe Trp Asp 
225                 230                 235                 240 


Tyr Val Ser Leu Gln Pro Glu Thr Leu His Asn Val Met Trp Ala Met 
                245                 250                 255     


Ser Asp Arg Gly Ile Pro Arg Ser Tyr Arg Thr Met Glu Gly Phe Gly 
            260                 265                 270         


Ile His Thr Phe Arg Leu Ile Asn Ala Glu Gly Lys Ala Thr Phe Val 
        275                 280                 285             


Arg Phe His Trp Lys Pro Leu Ala Gly Lys Ala Ser Leu Val Trp Asp 
    290                 295                 300                 


Glu Ala Gln Lys Leu Thr Gly Arg Asp Pro Asp Phe His Arg Arg Glu 
305                 310                 315                 320 


Leu Trp Glu Ala Ile Glu Ala Gly Asp Phe Pro Glu Tyr Glu Leu Gly 
                325                 330                 335     


Phe Gln Leu Ile Pro Glu Glu Asp Glu Phe Lys Phe Asp Phe Asp Leu 
            340                 345                 350         


Leu Asp Pro Thr Lys Leu Ile Pro Glu Glu Leu Val Pro Val Gln Arg 
        355                 360                 365             


Val Gly Lys Met Val Leu Asn Arg Asn Pro Asp Asn Phe Phe Ala Glu 
    370                 375                 380                 


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


Phe Thr Asn Asp Pro Leu Leu Gln Gly Arg Leu Phe Ser Tyr Thr Asp 
                405                 410                 415     


Thr Gln Ile Ser Arg Leu Gly Gly Pro Asn Phe His Glu Ile Pro Ile 
            420                 425                 430         


Asn Arg Pro Thr Cys Pro Tyr His Asn Phe Gln Arg Asp Gly Met His 
        435                 440                 445             


Arg Met Gly Ile Asp Thr Asn Pro Ala Asn Tyr Glu Pro Asn Ser Ile 
    450                 455                 460                 


Asn Asp Asn Trp Pro Arg Glu Thr Pro Pro Gly Pro Lys Arg Gly Gly 
465                 470                 475                 480 


Phe Glu Ser Tyr Gln Glu Arg Val Glu Gly Asn Lys Val Arg Glu Arg 
                485                 490                 495     


Ser Pro Ser Phe Gly Glu Tyr Tyr Ser His Pro Arg Leu Phe Trp Leu 
            500                 505                 510         


Ser Gln Thr Pro Phe Glu Gln Arg His Ile Val Asp Gly Phe Ser Phe 
        515                 520                 525             


Glu Leu Ser Lys Val Val Arg Pro Tyr Ile Arg Glu Arg Val Val Asp 
    530                 535                 540                 


Gln Leu Ala His Ile Asp Leu Thr Leu Ala Gln Ala Val Ala Lys Asn 
545                 550                 555                 560 


Leu Gly Ile Glu Leu Thr Asp Asp Gln Leu Asn Ile Thr Pro Pro Pro 
                565                 570                 575     


Asp Val Asn Gly Leu Lys Lys Asp Pro Ser Leu Ser Leu Tyr Ala Ile 
            580                 585                 590         


Pro Asp Gly Asp Val Lys Gly Arg Val Val Ala Ile Leu Leu Asn Asp 
        595                 600                 605             


Glu Val Arg Ser Ala Asp Leu Leu Ala Ile Leu Lys Ala Leu Lys Ala 
    610                 615                 620                 


Lys Gly Val His Ala Lys Leu Leu Tyr Ser Arg Met Gly Glu Val Thr 
625                 630                 635                 640 


Ala Asp Asp Gly Thr Val Leu Pro Ile Ala Ala Thr Phe Ala Gly Ala 
                645                 650                 655     


Pro Ser Leu Thr Val Asp Ala Val Ile Val Pro Cys Gly Asn Ile Ala 
            660                 665                 670         


Asp Ile Ala Asp Asn Gly Asp Ala Asn Tyr Tyr Leu Met Glu Ala Tyr 
        675                 680                 685             


Lys His Leu Lys Pro Ile Ala Leu Ala Gly Asp Ala Arg Lys Phe Lys 
    690                 695                 700                 


Ala Thr Ile Lys Ile Ala Asp Gln Gly Glu Glu Gly Ile Val Glu Ala 
705                 710                 715                 720 


Asp Ser Ala Asp Gly Ser Phe Met Asp Glu Leu Leu Thr Leu Met Ala 
                725                 730                 735     


Ala His Arg Val Trp Ser Arg Ile Pro Lys Ile Asp Lys Ile Pro Ala 
            740                 745                 750         


<210>  5
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  5

Ala Ser Gly Ala Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly Thr 
1               5                   10                  15      


Ser Gly Ala Thr 
            20  


<210>  6
<211>  270
<212>  PRT
<213>  Aerococcus viridans


<220>
<221>  MISC_FEATURE
<223>  lactate oxidase

<400>  6

Asn Asn Asn Asp Ile Glu Tyr Asn Ala Pro Ser Glu Ile Lys Tyr Ile 
1               5                   10                  15      


Asp Val Val Asn Thr Tyr Asp Leu Glu Glu Glu Ala Ser Lys Val Val 
            20                  25                  30          


Pro His Gly Gly Phe Asn Tyr Ile Ala Gly Ala Ser Gly Asp Glu Trp 
        35                  40                  45              


Thr Lys Arg Ala Asn Asp Arg Ala Trp Lys His Lys Leu Leu Tyr Pro 
    50                  55                  60                  


Arg Leu Ala Gln Asp Val Glu Ala Pro Asp Thr Ser Thr Glu Ile Leu 
65                  70                  75                  80  


Gly His Lys Ile Lys Ala Pro Phe Ile Met Ala Pro Ile Ala Ala His 
                85                  90                  95      


Gly Leu Ala His Thr Thr Lys Glu Ala Gly Thr Ala Arg Ala Val Ser 
            100                 105                 110         


Glu Phe Gly Thr Ile Met Ser Ile Ser Ala Tyr Ser Gly Ala Thr Phe 
        115                 120                 125             


Glu Glu Ile Ser Glu Gly Leu Asn Gly Gly Pro Arg Trp Phe Gln Ile 
    130                 135                 140                 


Tyr Met Ala Lys Asp Asp Gln Gln Asn Arg Asp Ile Leu Asp Glu Ala 
145                 150                 155                 160 


Lys Ser Asp Gly Ala Thr Ala Ile Ile Leu Thr Ala Asp Ser Thr Val 
                165                 170                 175     


Ser Gly Asn Arg Asp Arg Asp Val Lys Asn Lys Phe Val Tyr Pro Phe 
            180                 185                 190         


Gly Met Pro Ile Val Gln Arg Tyr Leu Arg Gly Thr Ala Glu Gly Met 
        195                 200                 205             


Ser Leu Asn Asn Ile Tyr Gly Ala Ser Lys Gln Lys Ile Ser Pro Arg 
    210                 215                 220                 


Asp Ile Glu Glu Ile Ala Gly His Ser Gly Leu Pro Val Phe Val Lys 
225                 230                 235                 240 


Gly Ile Gln His Pro Glu Asp Ala Asp Met Ala Ile Lys Arg Gly Ala 
                245                 250                 255     


Ser Gly Ile Trp Val Ser Asn His Gly Ala Arg Gln Leu Tyr 
            260                 265                 270 


<210>  7
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  7

Gly Gly Gly Ser 
1               


<210>  8
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  8

Gly Gly Gly Gly Ser 
1               5   


<210>  9
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Albumin Binding Peptide (ABP)

<400>  9

Asp Ile Cys Leu Pro Arg Trp Gly Cys Leu Glu Trp Glu Asp 
1               5                   10                  


