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- W4285387776 abstract "RNA-based macromolecular machines, such as the ribosome, have functional parts reliant on structural interactions spanning sequence-distant regions. These features limit evolutionary exploration of mutant libraries and confound three-dimensional structure-guided design. To address these challenges, we describe Evolink (evolution and linkage), a method that enables high-throughput evolution of sequence-distant regions in large macromolecular machines, and library design guided by computational RNA modeling to enable exploration of structurally stable designs. Using Evolink, we evolved a tethered ribosome with a 58% increased activity in orthogonal protein translation and a 97% improvement in doubling times in SQ171 cells compared to a previously developed tethered ribosome, and reveal new permissible sequences in a pair of ribosomal helices with previously explored biological function. The Evolink approach may enable enhanced engineering of macromolecular machines for new and improved functions for synthetic biology." @default.
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- W4285387776 date "2022-07-14" @default.
- W4285387776 modified "2023-10-16" @default.
- W4285387776 title "Three-dimensional structure-guided evolution of a ribosome with tethered subunits" @default.
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- W4285387776 doi "https://doi.org/10.1038/s41589-022-01064-w" @default.
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