Computational Aminoacyl-tRNA Synthetase Library Design for Photocaged Tyrosine

  title={Computational Aminoacyl-tRNA Synthetase Library Design for Photocaged Tyrosine},
  author={Tobias Baumann and Matthias Hauf and Florian Richter and Suki Albers and Andreas M{\"o}glich and Zoya Ignatova and Nediljko Budisa},
  journal={International Journal of Molecular Sciences},
Engineering aminoacyl-tRNA synthetases (aaRSs) provides access to the ribosomal incorporation of noncanonical amino acids via genetic code expansion. Conventional targeted mutagenesis libraries with 5–7 positions randomized cover only marginal fractions of the vast sequence space formed by up to 30 active site residues. This frequently results in selection of weakly active enzymes. To overcome this limitation, we use computational enzyme design to generate a focused library of aaRS variants… Expand
8 Citations
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Engineering aminoacyl-tRNA synthetases for use in synthetic biology.
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Integration of Machine Learning Improves the Prediction Accuracy of Molecular Modelling for M. jannaschii Tyrosyl-tRNA Synthetase Substrate Specificity
A novel workflow through integration of molecular modeling and data-driven machine learning method to generate mutant libraries with high enrichment ratio for recognition of specific substrate and it is found D158G/P is the critical residue which influences the backbone disruption of helix with residue 158-163. Expand
Combating Antimicrobial Resistance With New-To-Nature Lanthipeptides Created by Genetic Code Expansion
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Current computational methods for enzyme design
Computational enzyme design has made great strides over the last five years. Traditional methods of enzyme design require synthesis and evaluation of many mutations. Computational enzyme design has...


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Phage-assisted continuous evolution selections are designed to rapidly produce highly active and selective orthogonal AARSs with high activity and amino acid specificity and the capability of PACE is established to efficiently evolve orthogsonal Aarss withHigh activity and Amino acid specificity. Expand
Structural diversity and protein engineering of the aminoacyl-tRNA synthetases.
A suggested general approach to rational design is presented, which should yield insight into the identities of the protein-RNA motifs at the heart of the genetic code, while also offering a basis for improving the catalytic properties of engineered tRNA synthetases emerging from genetic selections. Expand
Polyspecific pyrrolysyl-tRNA synthetases from directed evolution
Structural and biochemical data reveal the molecular basis of polyspecificity in AcKRS and in a PylRS variant that displays both enhanced activity and substrate promiscuity over a chemical library of 313 ncAAs and suggest that translation fidelity will become an increasingly dominant factor in expanding the genetic code far beyond 20 amino acids. Expand
Reassignment of sense codons: Designing and docking of proline analogs for Escherichia coli prolyl-tRNA synthetase to expand the genetic code
Amino acyl-tRNA synthetases (AARSs) play a vital role in protein synthesis by catalyzing the aminoacylation of tRNA with its cognate amino acid. More recently, the endogenous AARS has been reportedExpand
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Importance of single molecular determinants in the fidelity of expanded genetic codes
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A Mutant Escherichia coli Tyrosyl-tRNA Synthetase Utilizes the Unnatural Amino Acid Azatyrosine More Efficiently than Tyrosine*
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