Proteins with extended or alternative backbones represent the next frontier in protein and biomaterial evolution. One extended backbone of great interest includes β-esters found in natural products and bioplastics. In this paper, the authors report that β2-hydroxy acids possessing both (R) and (S) absolute configuration are excellent substrates for pyrrolysyl-tRNA synthetase (PylRS) enzymes in vitro, and that (S)-β2-hydroxy acids are substrates in cellulo. Using the MaPylRS/MatRNAPyl pair, we report the cellular synthesis of model proteins containing two (S)-β2-hydroxy acid residues at internal positions.
This work is a collaboration between the Schepartz lab, Ara Abramyan of Schrödinger, and the Amgen Process Development group.
Read the paper: https://pubs.acs.org/doi/10.1021/acscentsci.3c01366