Modified beta-lactamases and methods and uses related thereto
The present invention relates to pharmaceuticals and modified beta-lactamases. Specifically, the invention relates to novel recombinant beta-lactamases and pharmaceutical compositions comprising the beta-lactamases. Also, the present invention relates to methods for modifying a beta-lactamase, producing the beta-lactamase and treating or preventing beta-lactam antibiotic induced adverse effects. Furthermore, the present invention relates to the beta-lactamase for use as a medicament and to the use of the beta-lactamase in the manufacture of a medicament for treating or preventing beta-lactam antibiotics induced adverse effects. Still further, the invention relates to a polynucleotide and a host cell comprising the polynucleotide.
1. A composition, comprising a beta-lactamase comprising an amino acid sequence having at least 97% sequence identity with SEQ ID NO: 1 and a hydrophilic amino acid residue other than aspartic acid (D) at a position corresponding to position 276 according to Ambler classification, wherein the hydrophilic amino acid residue is selected from asparagine (N) and arginine (R).
2. The beta-lactamase according to claim 1 , wherein the hydrophilic amino acid residue is located in an alpha helix.
3. The beta-lactamase according to claim 1 , wherein the beta-lactamase further comprises at least one amino acid selected from a leucine (L) at a position corresponding to position 220 and an arginine (R) at a position corresponding to position 244 according to Ambler classification.
4. The beta-lactamase according to claim 1 , wherein the beta-lactamase hydrolyzes a penicillin and a cephalosporin.
5. The beta-lactamase according to claim 4 , wherein the cephalosporin is selected from cefoperazone and ceftriaxone.
6. The beta-lactamase according to claim 1 , wherein the beta-lactamase comprises an amino acid sequence having at least 98% sequence identity with SEQ ID NO: 1.
7. The beta-lactamase according to claim 1 , wherein the beta-lactamase comprises an amino acid sequence having at least 99% sequence identity with SEQ ID NO: 1.
8. A pharmaceutical composition for oral administration comprising an effective amount of a beta-lactamase comprising an amino acid sequence having at least 97% sequence identity with SEQ ID NO: 1 and a hydrophilic amino acid residue other than aspartic acid (D) at a position corresponding to position 276 according to Ambler classification, wherein the hydrophilic amino acid residue is selected from asparagine (N) and arginine (R).
9. The pharmaceutical composition according to claim 8 , wherein the beta-lactamase comprises an amino acid sequence of at least 98% sequence identity with SEQ ID NO: 1.
10. The pharmaceutical composition according to claim 8 , wherein the beta-lactamase comprises an amino acid sequence of at least 99% sequence identity with SEQ ID NO: 1.
11. The pharmaceutical composition according to claim 8 , wherein the beta-lactamase hydrolyzes a penicillin and a cephalosporin.
12. The pharmaceutical composition according to claim 11 , wherein the cephalosporin is selected from cefoperazone and ceftriaxone.