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US 12,735,686 B2Granted
Enzymatic degradation of polyethylene terephthalate
AssigneeBioMetis Technology, Inc.
InventorsJie Yang, Xiyun Zhang, Khin Oo, Goutami Banerjee
Life of this patent
Estimating the term…
Abstract
The present disclosure provides variant enzymes for use in the enzymatic degradation of polyethylene terephthalate (PET).
Claims11
A composition comprising a variant bacterium HR29 polyethylene terephthalate hydrolase (Bhr-PETase) as compared to SEQ ID NO:1,
- wherein said variant has PETase activity greater than SEQ ID NO:1, and
- said variant Bhr-PETase comprises a set of amino acid substitutions selected from the group consisting of
- P20T/L90Y/F92L/S101M/D158E/A174K/I222L,
- P20T/F21W/A24V/L90Y/F92L/T109K/A125S/T136A,
- R12K/S32K/L90Y/F92L/T136A/A174K/D203V/I222L,
- R12K/A14K/V23T/L90Y/F92G/S101A/D203R,
- T17G/S32M/L90Y/F92Y/D203R/A216P,
- P20T/F21W/S32M/L90Y/F92G/A114K/A125S/
- T136V/D158E/A174K/D203V/I222L,
- T17Q/L90Y/F92L/A174K/D203V/I222L,
- T17S/D18R/L90Y/F92G/A114V/A117Q/D203R,
- L90Y/F92L/S101A/S110R/A125S/Q142W/A174R/A216P,
- S32K/L90Y/F92G/A114K/D203V,
- T17C/L90Y/F92L/S101N/T109L/S110R/A125S/A174K/D203R,
- T17C/L90Y/F92L/A125S/T136V/D158E/A174K,
- L90Y/F92L/S110R/A125S/D158E/D203V,
- T17Q/L90Y/F92L/T109L/T136A/D158E/A174R/D203V/V229C,
- P20T/F21W/S32M/L90Y/F92G/T109L/S110R,
- A14K/S32M/L90Y/S101R/A114V/T136A/A216P,
- P20T/F21W/L90Y/F92G/A125S/
- A174K/V229I, S32K/L90Y/F92Y/S101A,
- D18R/S32Q/N87H/L90Y/F92G/S101K/Q142L/D158I/A174R,
- T17Q/L90Y/F92G/S101N/T109L/
- S110R/T136V/Q142L/D203V/A216P,
- S32Q/L90Y/F92L/T109K/A125S/T136V,
- P20T/L90Y/T109K/T136A/D158I/D203R,
- N2R/S32Q/L90Y/F92Y/T109K/D203V,
- T17H/A24V/S32Q/L90Y/F92L/
- S101H/A114K/D158I/A174R/D203V,
- V23T/A24V/L90Y/F92G/A125S/T136V/D203V,
- P20T/S32K/L90Y/F92G/S101N/T109L/
- S110R/A125S/A174K/D203R/A216P,
- R12K/A14K/A24V/N87L/L90Y/A125S/
- T136V/A216P, P20T/F21W/L90Y/A125S,
- N2R/L90Y/A114K/A117Q/D203V/V229I,
- F21W/S32K/L90Y/A125S/D158E/A216P/V229I, S27L/T136V,
- S27L/P8T/T17Q/F21W/S101A/T136V/Q142L,
- S27L/N2R/T17L, S27L/V23T/A24V/T136A/Q142W,
- S27L/F21W/T136V, S27L/T17Q/T109K/A114K/T136V/V229I,
- S27L/T17Q, S27L/T136V/I222L/V229C,
- S27L/T17A/A114V/A117N/T136A, S27L/N2R/T136A,
- S27L/N2R/T17A, S27L/T17C/S101A/T136V,
- S27L/P20T/T136A, S27L/T136V/Q142W/V229I,
- S27L/T109K/T136V/I222L/V229I,
- S27L/T17L/S101H/A117N/Q142L/I222L/V229I,
- S27L/S101Q/T109L/A117N/T136A/Q142L,
- S27L/T109K/S110R/S193N/S252T/
- R255M, S27L/S22R/Y26K/R236Q,
- S27L/L90F/F92L/S98E/S113Y/A114K/T136A/
- D158E/S181R/T206G/S212M/V219I,
- S27L/N9S/S22P/T48N/L90Y/F92G/T109K/
- S110R/T136A/Q189V/N211F/R236Q,
- S27L/T17A/Y26L/T48N/I82M/S101D/R236Q,
- S27L/Y26T/S101D/D158E/V219I/S252T,
- S27L/S13R/S98E/T136V/S181R/T206G/V229I/N231S,
- S27L/F21W/F92L/S98N/S193P/I222L,
- S27L/S1G/Y26K/L90Y/S113Y/A114V/
- T136A/Q189V/N204R/N211L/R236Q,
- S27L/S22K/I82L/L90Y/F92G/R108S/A117N/D158E/S193N,
- S27L/S1G/N9S/T48S/L90Y/S98T/S101A/
- S113N/A114K/L119M/S193N/T206G/S252T,
- S27L/N9E/R12K/S22P/V23L/T160R/D203R/I222L,
- S27L/N9E/R12K/S22P/V23T/T48S/S98E/
- R108S/T160S/Q189V/T206G/S212L/V229I,
- S27L/S1A/N2R/N9S/T48N/L90F/F92L/D203V/S223A,
- S27L/N9E/R12K/V23T/I82M/L90Y/
- F92L/T136V/N204K/N231S/R255M,
- S27L/S1G/N9S/S22V/I82F/L90Y/F92L/
- A117N/L119M/Q142L/T206G/S212L/S223A,
- S27L/N9S/Y60H/R108C/S193P/V219L,
- S27L/N9E/S22K/S32M/L90F/F92G/R108T/
- L119M/Q189V/I222L/S223A/R236Q,
- S27L/T17Q/F92G/S98N/Q142L/Q189L/R236C,
- S27L/N9E/R12K/Q142W/T160Q/T206G/S212M,
- S27L/Y26T/S113N/A114V/T136A/D158E/
- D203R/N211F/R236Q/S252T/R255M,
- S27L/S1A/T17H/S22V/L90Y/F92G/S98E/A114V/T136A,
- S27L/N9E/T48S/I82M/L90Y/F92L/N122A/A127S/
- T160S/A174R/T206G/S212L/R255M,
- S27L/N9S/S22P/V23L/L90Y/F92G/A125S/
- T160S/N204R/I222L/S223A/R236Q,
- S27L/N9E/S22P/T48S/L90Y/F92L/
- T109R/E173R/A174K/D203V/S223A,
- S27L/R12K/Y26K/T48N/I82L/L90F/A125S/N211I/A216P,
- S27L/N9S/R12K/F92Y/T109K/S110R/
- T160K/Q189L/S223A/S252T/R255M,
- S27L/S1A/N2R/N9E/R12K/S32K/N87F/
- R108T/N211I/V219K/R255M,
- S27L/L90F/F92G/N122A/T136A/T160V/E173R/D203R/S252T,
- S27L/L90Y/F92G/S98T/T109L/D158I/S193K/
- V219K/R236Q/S252T,
- S27L/N9E/R12K/T48N/L90F/S98L/R108Q/
- A117Q/T136A/T206G/S212F/V219I/V229I/R255L,
- S27L/S1A/S22V/N87K/R108K/
- N122E/D158E/S193P/V219I/R255M,
- S27L/F21W/Y26T/S34R/R108H/L119M/N211M/R236C/S252T,
- S27L/S1A/N9E/R12K/V23T/T48S/N87H/S101Q/
- Q189L/N211M/V219/R236Q/R255M,
- S27L/N9S/T25Q/L90Y/S101D/T136A/Q142L/Q189L/R236Q,
- S27L/A14K/I82F/F92G/S98E/R108C/A117N/
- L119M/Q189V/T206G/I222L/S223A,
- S27L/T17C/Y26T/N87V/R108C/
- N122E/T136V/S193P/S252T/R255M,
- S27L/L90Y/F92G/T109L/N122S/R255M,
- S27L/R12K/L90Y/T160V/A174R/R236Q,
- S27L/N9E/R12K/T48N/L90Y/F92G/S98T/S113R/
- N122R/A127S/T136A/A174K/N204K/S212L,
- S27L/V23T/L90Y/F92G/S98E/T109L/A125S/T160V/
- A174K/S181C/S193K/T206G/S212M/R255M,
- S27L/A24V/F92G/S101D/A114V/A117N/A125S/
- T136V/D203R, S27L/R12K/S32Q/S101Q,
- S27L/L90F/F92G/T136V/A174R/D203R,
- S27L/P20T/S32K/L90Y/D203V,
- S27L/N2R/A14K/T17S/L90Y/T109K/T136V/A216P,
- S27L/N2R/V23T/A24V/S32M/L90Y/F92G,
- S27L/A14K/L90Y/F92L/S101D/A117N/D158I/D203R,
- S27L/F21W/N87H/A114V/A117N/T136V,
- S27L/N2R/V23T/A24V/N87M/F92L/S101K/A125S/T136A,
- S27L/L90Y/F92L/S101N/T109R/S110R/
- Q142W, S27L/S32M/F92G/A216P,
- S27L/F21W/L90Y/F92L/A114K/A117N/T136A/D203V,
- S27L/N2R/V23T/S32M/N87M/F92L/T136A,
- S27L/R12K/L90F/F92G/S101A/
- D203V, S27L/A24V/L90F/F92G,
- S27L/R12K/F92L/S101A/A125S/T136A/D203R,
- S27L/R12K/V23L/L90F/F92L/A114K/T136A/
- D158E/D203V/I222L, S27L/L90F/F92G,
- S27L/A14K/P20T/S32Q/L90Y/A125S/D203V,
- S27L/T17L/L90F/F92G/A125S/A174R/D203V,
- S27L/N2R/N87K/A114K/A117Q/T136V/D203V,
- S27L/N2R/A114K/T136V/D203V,
- S27L/N2R/T17A/T136V/A216P, S27L/N2R/
- R12K/N87F/T136V/D158E/A174R, S27L/D203R,
- S27L/R12K/T17Q/T136V/D203V/
- A216P, S27L/N87F/T109L/Q142L,
- S27L/N2R/T17Q/A24V/A114K/A117Q/
- T136A/D158E/A174K/D203V/I222L,
- S27L/N2R/P20T/F21W/N87M/T109R/
- A117N/A125S/T136V/D203V/I222L,
- S27L/V23T/A24V/T136A/D158E/A174K/D203V/I222L,
- S27L/R12K/V23L/A114K/T136A/D158/D203V/I222L,
- S27L/N87Y/T136V/D158E/D203V,
- S27L/T109K/S110R/D203R, S27L/N2R/T17L/A125S/
- T136A/D158E, S27L/A24V/D158E/A174K/A216P,
- S27L/T17G/V23L/N87L/A117Q/A125S/T136V/D158E/V229C,
- S27L/V23L/N87L/T109R/A114K/A117N/A125S/T136V/Q142L,
- S27L/N87Y/S101A/A114V/A117Q/T136V/
- A174K/A216P/I222L, S27L/R12K/T109R/Q142L,
- S27L/D203V, S27L/T17G/N87F/S101A/D203V,
- S27L/T17L/N87M/Q142L/D203V,
- S27L/N2R/R12K/S101D/A117N/T136A/D203V,
- S27L/R12K/P20T/F21W/A114K/Q142W/D203R,
- S27L/N2R/T17G/T109L/S110R/A114K/A117Q/
- T136V/Q142L/D203R, S27L/N2R,
- S27L/S32K/L90F/F92G/S101M/A114V/
- A117N/A125S/T136A/D158E/D203V,
- S27L/R12K/T17A/F21W/S32Q/Y60H/D203R,
- S27L/R12K/F92L/S110R/T136V/I222L,
- S27L/A14K/V23T/A24V/L90Y/F92G/
- A114V/A117Q/Q142L/A174R/I222L,
- S27L/F21W/S32Q/L90Y/S101D/T109K/A125S/T136A/A174K,
- S27L/V23T/L90Y/F92G/T136A/D203V/A216P,
- S27L/T17S/L90Y/F92G/A117N/T136A/D158L,
- S27L/A14K/V23L/A24V/F92L/Q142W/D203V,
- S27L/T17L/L90F/F92G/S101K/A174K,
- S27L/L90F/F92L/A125S/T136V/A174K/D203V/A216P/I222L,
- S27L/R12K/P20T/S32M/L90F/F92G/S101M/A114V/D203V,
- S27L/T17A/S32Q/L90F/F92L/T136V/Q142W/A174K/D203R,
- S27L/R12K/S32M/L90F/F92G/S101W/A114V/D158I/I222L,
- S27L/P20T/S32M/L90Y/F92L/A114V/A117N/I222L,
- S27L/T17C/L90Y/F92G/T136A/A174K/D203V,
- S27L/S32Q/N87Y/F92G/T109K/
- A114K/A117N/T136V/D203V/V229C,
- S27L/F21W/L90F/F92G/T136V/A174R,
- S27L/P20T/N87Y/T136A/D203V/I222L,
- S27L/A24V/L90Y/F92L/D158I/A174K/D203R/I222L,
- S27L/F21W/S32Q/L90Y/S110R/A114K/T136V/
- D203R/A216P/V229I, S27L/N87H/F92G/D203R,
- S27L/R12K/S32K/Y60A/A125S/T136V/D158L,
- S27L/V23T/A24V/S32Q/L90F/F92L/T136A,
- S27L/F92L/A114V/D158E/D203R,
- S27L/S32Q/L90Y/D203V/V229I,
- S27L/V23T/S32Q/Y60H/T109K/T136V/A216P/I222L,
- S27L/A14K/A24V/L90F/F92G/T109K/
- T136V/D158L/A174R/D203V/I222L/V229I,
- S27L/R12K/N87F/A174K, S27L/P20T/S32Q/
- Y60H/T109K/A114V/T136A/A174K,
- S27L/V23T/A24V/Y60A/A125S/A174R/
- A216P, S27L/F92Y/D158L/I222L,
- S27L/V23L/A24V/L90Y/F92G/D203V/I222L,
- S27L/V23T/A24V/S32Q/L90F/F92G/S101H/T136A/
- A174K/D203V/V229C, S27L/S32K/N87H/A125S,
- S27L/P20T/F21W/F92G/A114V, S27L/T17L/V23L/
- A24V/L90Y/F92L/A117N/T136V/L137M/Q142L,
- S27L/P20T/L90Y/D203R, S27L/S110R/
- Q142L/D158|/D203R/V229I,
- S27L/P20T/S32Q/L90F/F92L/T109K/S110R/A125S/D203V,
- S27L/V23T/A24V/L90F/F92G/D158E/D203R,
- S27L/F92G/T136A/A174R/D203V/V229C,
- S27L/P20T/L90Y/F92G/T109R/S110R/A125S/D203R,
- S27L/A14K/L90Y/F92L/D158L/A174R/D203V,
- S27L/F21W/S32Q/L90Y/F92G/T109L/
- S110R/A117N/D158I/A174K/D203V,
- S27L/R12K/A114K/A117N/D158E/D203V,
- S27L/T17S/N87H/T109R/A114K/A117N/T136V/
- Q142W/D203V, S27L/N2R/N87Y,
- S27L/T17S/V23T/A24V/S32Q/Y60H/N87K/T136A/D203R,
- S27L/P20T/F92Y/T109K/D158E/D203V,
- S27L/S32K/N87M/F92L/S101M/T109L/S110R/D203V,
- S27L/L90Y/F92G/T136A/D158E/D203V/
- A216P/V229I, S27L/A14K/S32M/F92L/A125S,
- S27L/L90Y/F92G/T136V/D158L/D203V,
- S27L/A24V/L90Y/F92G/S101A/T109L/
- S110R/A117Q/A174R/D203R,
- S27L/P20T/S101D/A114V/T136V/
- Q142W/D158E/D203R/A216P,
- S27L/N87Y/F92G/S101Q/A114K/A117N/
- T136A/D158L/D203R/A216P,
- S27L/V23T/A24V/N87Y/L90Y/F92L/
- S101D/T109R/A174K/D203R/A216P,
- S27L/N2R/P20T/F21W/L90F/F92Y, S27L/
- L90Y/F92G/D158I/D203V/V229C,
- S27L/S32Q/F92G/Q142W/I222L, S27L/N2R/
- R12K/S32M/N87Q/L90F/F92L/I222L,
- S27L/R12K/S32K/F92L/A114V/A117Q/
- T136A/D158E/A216P, S27L/L90Y/F92G,
- S27L/R12K/F21W/S32M/F92G/T136V/Q142L/D203R,
- S27L/R12K/A14K/L90Y/F92L/A125S/A174K,
- S27L/A24V/A114V/A117Q/T136V/D203V,
- S27L/R12K/T17Q/V23L/S32M/
- L90Y/F92G/S101D/T136V/I222L,
- S27L/V23T/A24V/S32Q/F92L/S101N/T109L/S110R/D203R,
- S27L/P20T/Y60H/N87K/T136A/A174R/D203V,
- S27L/P20T/F21W/L90Y/F92L/T136A/A174R/D203V/V229C,
- S27L/T17G/F21W/S32K/L90F/F92G/A125S/T136A/
- A174K, S27L/T17G/N87Y/T136A/D203V/A216P,
- S27L/F21W/L90F/F92G/S101D/A117N/T136A/
- A174K/D203V, S27L/R12K/A14K/A24V/L90Y/D203V,
- S27L/N2R/L90F/F92G/S101M/Q142L/D158L,
- S27L/N2R/T17C/A24V/N87K/A174K/A216P,
- S27L/N87M/Q142L/I222L, S27L/F92L/S98T/R108C/
- A117Q/A127S/Q142L/Q189V/A216P/R236Q,
- S27L/S22K/F92L/R108H/A127S/T136A/N211I,
- S27L/F21W/T48S/L90Y/F92L/T109L/
- A127S/T136V/N204K/S223A,
- S27L/T17L/L90Y/F92L/S98M/A174K/D203V/
- N211M/S212L/S223A, S27L/N87K/S98M/N211M,
- S27L/N9E/S22P/L90Y/N204K, S27L/
- S32M/T48S/F92G/A127S/Q142W,
- S27L/T17S/S22K/L90F/F92L/D158E/D203V/V219/
- S252T, S27L/L90F/F92L/A127S/D203V,
- S27L/T25F/L90Y/F92G/N204R/S223A/N231S/R236C,
- S27L/F21W/S22V/T48S/L90F/F92L,
- S27L/S1A/S98T/S113K/A114V/L119M/A127S/
- Q142W/S193K/V219K/S252T/R255L,
- S27L/A24V/I82L/L90F/F92G/T109L/
- L119M/A127S/E173R/N204K,
- S27L/T17C/Y60H/L90F/A127S/E173R/A174R/N204K,
- S27L/L90F/F92L/Q142W/D203V/S223A,
- S27L/P20Q/L90Y/Q142L/S223A,
- S27L/N9S/Y60A/A216P/R236Q/R255M,
- S27L/F92G/R108C/S110R/A117Q/T136A/N211M,
- S27L/S22P/Y60H/S98A/S113K/A114K/T136V/Q189L/S193H,
- S27L/V23L/S98A/Q142L/N211M,
- S27L/V23L/Y26L/L31M/T48S/F92G/A174R/N204K/S252T,
- S27L/S13R/A14K/Y26T/T136A/S181R/N211M/S212M,
- S27L/F21W/I82F/L90Y/F92G/A127S/N211M,
- S27L/P20T/Y60H/S98L/T136A/R255L,
- S27L/P20T/S34R/N87M/D158E/S252T,
- S27L/T25A/L90F/F92G/Q189L/
- S193P/V229I, S27L/V219L/I222L,
- S27L/N9E/T48S/L90F/F92L/S98N/R108H/
- S110R/S113Y/N211V/S212L/S252T,
- S27L/L90F/F92Y/S113R/V219I/R255L,
- S27L/F21W/S22K/T48S/F92G/T109R/A127S,
- S27L/S1G/A14K/P20T/S32K/T48S/L90Y/F92L/
- T109L/T160R/V219L/I222L/S252T/R255L,
- S27L/L90F/F92G/D158E/T160R/S193N/N204K/S223A,
- S27L/A14K/Y26T/F92L/Q142L/S212L,
- S27L/S22R/L90Y/F92G/V126I/A127S/A174K/N204K,
- S27L/P20T/T25A/L90F/F92L/A117N/L119M/S252T/R255L,
- S27L/T17A/A24V/T48S/L90F/F92G/
- T109R/A127S/T160K/D203R/S223A,
- S27L/F21W/T48S/T109L/A127S/V219I/R255L,
- S27L/A14K/S22P/T48S/L90F/F92L/T109L/
- A127S/Q142L/A174R/N204K/S223A,
- S27L/T136A/S212M/N231S,
- S27L/F21W/L90F/F92G/A127S/S223A,
- S27L/T48S/L90Y/F92L/R108S/
- S110R/A127S/T136V/E173R/S223A,
- S27L/T48S/F92G/S98E/Q142L/Q189V/S193P/N204R/S223A,
- S27L/T17S/L90F/F92Y/S101K/A127S/
- T136V/N204R/N211I/V229I/N231S,
- S27L/N9E/F21W/T48S/L90Y/F92L/T109R/N204K/R236Q,
- S27L/N9E/S22R/T48S/F92L/S101N/A127S/E173R/N204R,
- S27L/S22K/N87F/A117Q/S181C/N204K/
- N211M/V229I/N231S/R236Q,
- S27L/N9S/T48S/L90F/F92G/S101N/
- A127S/N204K/A216P/S252T/R255M,
- S27L/I82L/S193H/N211M/S212F/S223A,
- S27L/A14K/P20T/T48S/L90F/F92G/S98N/R108C/
- T136A/N204K/N211L/S212L/R236Q/S252T,
- S27L/S13R/T17L/T25Q/L90F/F92G/
- R108C/A127S/T160R/I222L/R255L,
- S27L/T48S/L90Y/F92G/T109L/S193N,
- S27L/S22V/T48S/L90Y/F92L/S98E/A127S/
- T136A/N204K/A216P/S223A,
- S27L/V23L/N87H/F92L/R108C/S110R/N122A/
- T160S/Q189L/S193P/N204K/S223A/R255L,
- S27L/F92G/A127S/A174R/S223A/V229I/N231S/R236C,
- S27L/S1G/L90Y/A127S/E173R/S223A,
- S27L/F92Y/S98N/Q142W,
- S27L/P20T/S32M/S34R/T48S/L90Y/F92L/R108K/
- A127S/Q142W/A174R/N204K/V219I/S252T,
- S27L/F92G/A127S/Q189V/S193N/S223A,
- S27L/S34R/F92G/S110R/D158L/D203V/R255M,
- S27L/N9E/F21W/T48S/F92G/T109L/A127S/R236C,
- S27L/S1A/S22P/T48S/L90Y/F92G/
- A127S/E173R/A174R/N204K/S223A,
- S27L/S22K/T48S/T160S/N204K,
- S27L/F21W/T48S/L90Y/F92G/S98V/
- R108C/A127S/N211L/S212M/N231S/R236C,
- S27L/V23L/A24V/A114K/T136A/I222L/V229I,
- S27L/P20T/S101H/T109R/A114V/T136A/Q142L/I222L/V229I,
- S27L/V23L/S101H/T109K/A114K/
- A117N/T136V/Q142L/I222L/V229I,
- S27L/T17L/F21W/S101H/T109R/
- A114V/T136A/Q142L/I222L/V229I,
- S27L/T17S/T136V/Q142L/I222L/V229C,
- S27L/T17C/S22P/T48S/L90F/F92G/A127S/A174R/
- P192A/S193H/N204K/S223A/V229I/N231S/R236Q/
- R255L, S27L/N9E/T48N/N87H/F92L/
- A174K/Q189L/S193K/N204R/V219I,
- S27L/A14K/V23L/Y26L/L90F/F92G/S98E/
- S113K/A114K/T136A/V229I/N231S,
- S27L/L90Y/F92L/S101D/A117N/Q142L/S193N,
- S27L/S22K/T25A/L90Y/Q142L/E173R/N204K/S223A,
- S27L/P20T/L90Y/T109L/A127S/A174K/V229C,
- S27L/S22V/L90Y/F92L/A117Q/R236C/R255L,
- S27L/V23L/A24G/Y26T/I82F/L90Y/F92G/
- R108H/T136A/D158L/T160K/D203V,
- S27L/A14K/S22K/F92G/A127S/N204K/V229I,
- S27L/S22V/L90F/F92G/A127S/A174R/A216P/R236C,
- S27L/V23L/Y60A/S98T/T109L/A127S/
- T136V/T160Q/N204K/S223A/R255L,
- S27L/S13R/L90Y/S98L/T160V/Q189L/
- S193P/A216P/S252T/N253S/R255L,
- S27L/S22R/I82M/F92L/T109L/A127S/Q142W/Q189L/S223A,
- S27L/S1G/Y60A/L90F/F92L/N122E/
- T136A/N204K/S223A/N231S,
- S27L/S32K/F92G/S98L/R108Q/S110R/R255L,
- S27L/L90Y/F92G/L119M/A127S/A174R/S252T,
- S27L/L90F/S110R/S181R/N211F, S27L/A14K/S22P/
- Y60H/S110R/N122S/D158|/N204K/S223A/R255M,
- S27L/F92L/S98V/T109L/N122A/E173R/R255L,
- S27L/S22R/N87L/F92G/R236C,
- S27L/S32M/S34R/I82L/F92G/N204K/S223A,
- S27L/A24V/T25Q/Y60I/A127S/A174K/N204K/
- V219I/S223A/S252T/R255M, S27L/S98V/T136A/N211F,
- S27L/N9S/L90F/F92L/A127S/N204R/S212M,
- S27L/S22R/T48S/F92G/R108H/S110R/
- A127S/E173R/N204K/S223A/R236Q,
- S27L/A14K/L90Y/F92G/A127S, S27L/A14K/
- T48S/F92G/E173R/N204R/S223A/N231S,
- S27L/L90Y/T109R/S113N/V219L/I222L,
- S27L/N9S/T48S/L90Y/T136A/T206G/S223A,
- S27L/S22K/T48N/L90F/F92G/N204K/S223A/V229C/N231S,
- S27L/S22P/T48S/L90F/F92G/A127S/A174R/N204R/S223A,
- S27L/S1G/P20T/S32K/S34R/T48S/N87F/S98A/A127S/T136A,
- S27L/F21W/S22R/S98E/Q142L/T160V/S223A/S252T/R255L,
- S27L/P20T/T48S/F92Y/R108K/S110R/
- A127S/V219L/S223A/V229I/R236Q,
- S27L/Y26T/L90Y/F92L/A127S/V219L/S252T/R255L,
- S27L/N9S/F21W/T48S/F92L/A127S/D203V/S212F,
- S27L/F21W/Y60H/S98E/L119M/D158E/R236Q,
- S27L/F21W/S22R/L90F/F92L/N122S/Q142W/R236Q,
- S27L/F21W/T48S/L90F/F92G/T109K,
- S27L/L90Y/F92L/T109R/A127S/E173R/N204K/S223A,
- S27L/N9S/F21W/T48S/L90Y/F92G/
- A127S/N204K/V219I/R255M,
- S27L/N9E/I82F/L90Y/F92L/S95N/T109L/A127S/
- A174R/S223A, S27L/L90F/F92L/S98L/N204K/A216P,
- S27L/A24V/T48S/A117Q/N211M/S212M/S223A,
- S27L/L90Y/F92G/T109L/A127S/N204R/S223A,
- S27L/N2R/S32Q/N87K/A125S/V219L,
- S27L/S22P/T48S/L90F/F92L/S193N/V219L/S223A,
- S27L/T25Q/L119M/N211M/R236Q,
- S27L/L90Y/F92G/N122S/A127S/E173R/A216P/R236Q,
- S27L/P20T/S32K/L90F/F92G/N122E/
- D158E/T160S/Q189L/S223A/S252T,
- S27L/N9S/F21W/T48S/N87H/L90F/F92L/S113N/V229C,
- S27L/T25Q/I82L/L90F/F92G/S98L/
- S113R/A114V/T136A/S181R,
- S27L/P20T/R108Q/S110R/D203V/N211I,
- S27L/S1G/N2R/P20T/Y26T/S32M/T48S/
- L90Y/F92L/A127S/N204R/V219L,
- S27L/A14K/P20T/T48N/L90F/F92G/A117Q/A127S,
- S27L/N9S/T48N/L90Y/F92L/S98M/T109K/A127S/
- N204R/N211I/S212L/V219I,
- S27L/F21W/S22R/T48S/L90F/F92L/
- R108Q/A174K/N204K/S212F/S223A,
- S27L/S22R/Y60H/S98T/T136V/S193K/R236Q,
- S27L/S22K/Y26K/N87Y/L90Y/F92G/T109R/
- A127S/S252T/R255L, S27L/L90F/F92L/T109L,
- S27L/F21W/F92L/N204K/S252T/R255L,
- S27L/V23L/L90Y/F92G/A127S/S193K/
- N204R/V219I/R236C/R255L,
- S27L/F21W/L90Y/F92G/A114V/N122S/
- A127S/N204K/S223A/S252T,
- S27L/P20T/Y60A/T109L/Q189L/S212L,
- S27L/S22V/T48S/L90Y/F92G/N204K,
- S27L/S22V/S32K/T48S/I82F/F92G/A127S/N204K/S223A,
- S27L/A55L, S27L/A97V, S27L/F250L,
- S27L/T109G, S27L/G38D, S27L/A97S, S27L/A55V/A216T,
- S27L/P20D, S27L/A55V, S27L/T109Y,
- S27L/V165I, S27L/A184G, S27L/A97E, S27L/A184S,
- S27L/A97F, S27L/A97T, S27L/K197Y, S27L/A55I,
- S27L/A97P, S27L/A55M, S27L/P20E, S27L/A117L,
- S27L/T109L, S27L/K197T, S27L/T136S, S27L/A97L,
- S27L/T109A, S27L/P20I, S27L/L191V, S27L/A184C,
- S27L/A97Q, S27L/F250V, S27L/K197V,
- S27L/A117S, S27L/K197R, S27L/T109K, S27L/A55C,
- S27L/N2S/V177A, S27L/Q142D, S27L/G149C,
- S27L/F21Y, S27L/G149A, S27L/P164E, S27L/Y26C,
- S27L/T17N, S27L/S57M, S27L/D249I, S27L/T17S,
- S27L/P164T, S27L/Q142L, S27L/D249N, S27L/I185R,
- S27L/V83L, S27L/G149S, S27L/A24D,
- S27L/R251V, S27L/V83I, S27L/S110N, S27L/T17M,
- S27L/F161W, S27L/G46E, S27L/D249T, S27L/T17,
- S27L/S57C, S27L/S57T, S27L/S57L, S27L/Q167T,
- S27L/S57E, S27L/T17K, S27L/G149N, S27L/Q142E,
- S27L/S57F, S27L/T17A, S27L/P164H, S27L/T17R,
- S27L/G149T, S27L/R251T, S27L/S101Y, S27L/S57V,
- S27L/A24T, S27L/I185E, S27L/G46N, S27L/P164N,
- S27L/P164S, S27L/Q167V, S27L/F161V, S27L/S57I,
- S27L/G149D S27L/Q167I, S27L/I185Q,
- S27L/N2L/T17I/T136S/P164H/D249M,
- S27L/P20E/F21Y/I139T/P164H/K197T/R251E,
- S27L/A114V/A117N/T136A/I222L/V229I,
- S27L/P20T/A24V/S101Q/T109R/A117Q/I222L/V229I,
- S27L/S110D/A184S/K197T, S27L/T136S/D249T,
- S27L/F21Y/A184S, S27L/N2F/P20E/
- S110D/A184S/L191V/R251V,
- S27L/T17G/V23T/A24V/T109L/A117Q/T136A/
- I222L/V229I, S27L/P20D/F21Y/A55T/F250L/R251V,
- S27L/T109R/A117N/I222L/V229C,
- S27L/F21Y/A55T/T109A/A184S,
- S27L/V23L/A24V/S101K/A117N/I222L/V229C,
- S27L/S110K/A117Y/P164R, S27L/I139T/Q142E/I169V,
- S27L/A24H/R251V, S27L/F21W/A114V/T136A/I222L/
- V229I, S27L/N2S/A55V/I185Q/R251E,
- S27L/N2F/S101Y/Q142L/G149T/Q167I/I169C/V229L,
- S27L/N2F/S101C/A117F/P164S,
- S27L/Q142H/I185S/R251A, S27L/F21W/
- T109R/A117N/T136V/I222L/V229I,
- S27L/G46R/T109K/T136S/D249T, S27L/N2E/G46N/
- A55V/I185Y/D249I, S27L/V83L/F250V/R251E,
- S27L/F21W, S27L/S57C/R251E, S27L/V23L/
- A114V/A117N/T136A/I222L/V229I, S27L/A24N,
- S27L/T17A/P20T/S101Q/T109K/S110R/T136A/
- I222L/V229C, S27L/P164T/V165l/R251E,
- S27L/F21Y/G46E/A117T/T136S/G149C/R251Q,
- S27L/G46N/I139T/Q142E/P164T/I185A/V229L/F250V,
- S27L/V23L/T136A/I222L/V229I,
- S27L/V23T/A24V/T109K/A114K/A117Q/
- T136A/I222L/V229C, S27L/F250L/R251Q,
- S27L/P20E/F21Y/S57T/P164N/A184C/V229C,
- S27L/P20T/V23T/A24V/I222L/V229I,
- S27L/V83L/A97S/A184C/D249S, S27L/P20T/
- S101H/A114V/A117N/I222L/V229I, S27L/N2E/R251L,
- S27L/P20E/F21Y/S110D/A117S, S27L/T17A/
- V23T/A24V/T136A, S27L/P20D/S57E/S101C,
- S27L/N2S/V83L/A184S, S27L/T17S/S101N/
- T109K/A117N/T136V/Q142L/I222L/V229C,
- S27L/P20D/A55T/A117Y/K197R, S27L/P20T/I222L/
- V229C, S27L/T17I/A24D/S57I, S27L/N2F,
- S27L/T109K/A117N/T136V/I222L/V229C,
- S27L/N2L/A24T, S27L/N2F/P20I/F21Y/R251Q,
- S27L/N2F/G46E, S27L/T136V/Q142W/I222L/V229I,
- S27L/K197R/R251E, S27L/T17S/R251T,
- S27L/P20I/F21Y/A117F/I185G/D249N, S27L/
- T17L/S101M/T109K/S110R/A117Q/I222L/V229C,
- S27L/T17Q/T136A/I222L/V229C, S27L/V229I,
- S27L/T17A/F21W/S101Q/I222L/V229C,
- S27L/T17S/F21W/Q142L, S27L/T17L/T109L/
- S110R/A117Q/I222L/V229I, S27L/F21W/T136A,
- S27L/P20E/F21Y/G46E/V83L/A97Q,
- S27L/P20T/F21W/T136A/Q142L/I222L/V229I,
- S27L/T17G/F21W/A117N/I222L/V229I,
- S27L/F21W/T109K/S110R/T136A/V229I,
- S27L/T17C/T109K/A117N/T136A/I222L/V229I,
- S27L/P20T/T109L/S110R/A117N/I222L/V229I,
- S27L/A24N/P164S/K197V/R251T, S27L/
- V23L/A117Q, S27L/A55V/V83L/A117T,
- S27L/P20D/G46S/A55I/K197T, S27L/A117Y,
- S27L/F21W/S101M/I222L/V229C,
- S27L/N2L/T17N/S57C/S110D/A117L/
- P164N/I185G/V229L/R251T,
- S27L/N2E/G46S/V83L/T136S/A172T/V229C/D249N,
- S27L/P20T/T109R/A114K/A117Q/T136V/I222L/V229C,
- S27L/V23L/A24V/T136A/Q142W/I222L/V229I, S27L/N2L,
- S27L/T17A/F21W/T109R/S110R/I222L/V229I,
- S27L/T17C/A114K/A117N/T136V/I222L/V229I,
- S27L/V23L/I222L/V229C, S27L/S101N/A117Q/I222L,
- S27L/N2E/P20I/T109L/L191V/K197L/V229C,
- S27L/P20T/F21W/Q142W/I222L/V229C,
- S27L/N2L/G46E/T109K/F161V, S27L/T17S/V229I,
- S27L/T17Q/T136A/I222L/V229I,
- S27L/N2L/A172T, S27L/P20D/F21Y/F250V,
- S27L/N2L/A24H/A55C/V229L, S27L/N2L/P20E/F21Y/V229L,
- S27L/V23T/T109L/A114V/T136A/Q142L/I222L/V229C,
- S27L/P20T/F21W/I222L/V229C,
- S27L/T17H/F21W/T136V/Q142W/I222L/V229I,
- S27L/G46E/A55I/Q142E, S27L/N2F/R251Q,
- S27L/F21W/Q142L/I222L/V229C, S27L/I222L/V229I,
- S27L/P20T/S101M/A114V/A117N/Q142W/I222L/V229C,
- S27L/T17Q/A24V/S101W/T136A,
- S27L/N2S/P20D/A97C/A117F/F250L/R251E,
- S27L/S101M/A114V/A117Q/T136A, S27L/T163I,
- S27L/S101Q/Q142L/I222L/V229I, S27L/F21W/
- I222L/V229C, S27L/S101M/T136A/I222L/V229I,
- S27L/F21W/A24V, S27L/A24D/K197L,
- S27L/T17H/S110K, S27L/P20T/F21W/V229I,
- S27L/T17G/P20T/F21W/A117Q/I222L/V229C,
- S27L/F21W/A24V/A114V/A117Q/Q142W/I222L/V229C,
- S27L/P20T/A117Q/I222L/V229C,
- S27L/T17Q/V23T/A24V/I222L/V229I,
- S27L/N2F/D249N/F250L, S27L/V23T/Q142L/I222L/V229C,
- S27L/P20E/A24D/D249S/F250V,
- S27L/A24D/S110K, S27L/T109R/I222L/V229I,
- S27L/P20E/F21Y/K197T, S27L/T17A/V23L/
- S101M/T109K/S110R/A114V/A117Q/T136V/V229I,
- S27L/P20T/F21W/Q142W/I222L/V229I,
- S27L/F21W/I222L/V229I,
- S27L/P20T/V23T/A24V/T109L/S110R/
- I222L/V229I, S27L/A24D/L191F/R251Q,
- S27L/A24D/T136S/F250V, S27L/P20T/
- F21W/T109L/T136A/Q142W/I222L/V229C,
- S27L/N2E/I169L/F250L/R251Q,
- S27L/N2S/A24N/G46E/A55L/Q142D/V229C/R251L,
- S27L/N2E/P20E/F250V/R251L,
- S27L/N2F/P20E, S27L/A24V/V229C,
- S27L/P20D/F21Y/G46N/S110K/T163I/Q167V,
- S27L/P20T/T109K/A114K/Q142W/I222L/V229C,
- S27L/T17Q/S101D/T136A/I222L/V229I,
- S27L/F21W/T109R/A117N/T136V/Q142W/I222L/V229C,
- S27L/A24D/T109L/K197L, S27L/T17Q/Q142L/I222L/V229I,
- S27L/T17A/A24V/S101D/S110R/T136A,
- S27L/P20T/F21W/T109R/A117Q/T136V/Q142L/I222L/V229I,
- S27L/P20T/F21W/T109K/A117N/I222L/V229C,
- S27L/P20T/S101M/I222L/V229I,
- S27L/N2S/A24D/S101Y/P164E/V165I/I185E,
- S27L/T17N/A117S/V229L/R251A,
- S27L/S101W/A114V/T136V/V229C, S27L/P20D/
- G46N/A55C/S110N/T163I/A184S, S27L/A24H/G46E,
- S27L/T17H/S101Q/T136V/Q142L/V229C and
- S27L/V23T/A24V/I222L/V229C.
554 more elements
Dependencies are inferred from the claim text.