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SYNTHETIC BIOLOGY

Shackled ribosomes unleashed

Nature Chemical Biology volume 18, pages 918–920 (2022)Cite this article

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A directed evolution approach delivers ribosomes with highly functional tethered subunits. Combining the decoding and peptidyl transferase activities of the ribosome into a single entity sets the scene for more efficient protein engineering technologies.

In a seminal paper in 1968, Francis Crick explained the apparent immutability of the genetic code throughout evolution as a “frozen accident”1. It is now accepted that the genetic code had a single origin and was preserved in its current state, with minor exceptions, because primordial cells soon became dependent on the exact chemical composition of their early proteomes. Just like the code itself, the ribosome, the macromolecular machine that synthesizes proteins, has maintained its fundamental functional and structural features across all the kingdoms of life, including the fact that its two core activities — the decoding of genetic messages and the catalysis of peptide bonds — are separated into two subunits that need to come together to form a functional protein synthesizing machine. However, just as it was proven that the genetic code was actually malleable — enabling the insertion of over 70 different unnatural amino acids when appropriate directed evolution approaches were applied—the requirement for physical separation of the ribosomal subunits has also turned out to be an evolutionary eccentricity2. Now, using a new laboratory selection approach, Kim et al. have evolved a highly functional single-subunit ribosome with an improved ability to incorporate unnatural amino acids3.

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Fig. 1: Engineering of efficient tethered ribosomes via evolution and linkage (EvoLink).

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Authors and Affiliations

  1. Harry Perkins Institute of Medical Research, Nedlands, Western Australia, Australia

    Aleksandra Filipovska & Oliver Rackham

  2. ARC Centre of Excellence in Synthetic Biology, University of Western Australia Centre for Medical Research, Nedlands, Western Australia, Australia

    Aleksandra Filipovska & Oliver Rackham

  3. School of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, Australia

    Aleksandra Filipovska

  4. Telethon Kids Institute, Northern Entrance, Perth Children’s Hospital, Nedlands, Western Australia, Australia

    Aleksandra Filipovska & Oliver Rackham

  5. Curtin Medical School, Curtin University, Bentley, Western Australia, Australia

    Oliver Rackham

  6. Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia, Australia

    Oliver Rackham

Authors
  1. Aleksandra Filipovska
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  2. Oliver Rackham
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Correspondence to Oliver Rackham.

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The authors declare no competing financial interests.

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Filipovska, A., Rackham, O. Shackled ribosomes unleashed. Nat Chem Biol 18, 918–920 (2022). https://doi.org/10.1038/s41589-022-01020-8

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  • DOI: https://doi.org/10.1038/s41589-022-01020-8

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