Methods To Generate Novel Acyl-Trna Species
Tech ID: 32725 / UC Case 2022-095-0
Patent Status
| Country | Type | Number | Dated | Case |
| Patent Cooperation Treaty | Published Application | WO/2023/164676 | 08/31/2023 | 2022-095 |
Brief Description
The inventors have discovered PylRS enzymes that accept -thio acids, N-formyl-L-amino acids, and diverse -carboxyl acid monomers (malonic acids) that are formally precursors to polyketide natural products. These monomers are all accommodated and accepted by the translation apparatus in vitro. High-resolution structural analysis of the complex between one such PylRS enzyme and a meta-substituted 2-benzylmalonate derivative reveals an active site that discriminates pro-chiral carboxylates and accommodates the large size and distinct electrostatics of an -carboxyl acid substituent.
This discovery emphasizes the potential of PylRS for evolving new enzymes capable of encoding diverse non-L-amino acids in synergy with natural or evolved ribosomes. The absence of orthogonal aminoacyl-tRNA synthetase enzymes that accept non-L-amino acids is the primary bottleneck hindering the in vivo translation of sequence-defined hetero-oligomers.
Suggested uses
These enzymes could be used to develop keto-peptide hybrid molecules that are privileged scaffolds for drug design.
Advantages
Towards the goal of charging tRNAs with non-L-⍺-amino acid monomers, PylRS enzymes have advantages of MjTyrRS in how they recognize the ⍺-amine of their substrate.
Related Materials
Contact
- Laleh Shayesteh
- lalehs@berkeley.edu
- tel: View Phone Number.
Inventors
- Schepartz, Alanna S.
Other Information
Keywords
enzymes, in vivo
