Initiating ribosomal peptide synthesis with exotic building blocks
- 27 March 2020
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Chemical Communications
- Vol. 56 (31), 4265-4272
- https://doi.org/10.1039/d0cc01291b
Abstract
Ribosomal peptide synthesis begins almost exclusively with the amino acid methionine, across all domains of life. The ubiquity of methionine initiation raises the question; to what extent could polypeptide synthesis be realized with other amino acids, proteinogenic or otherwise? This highlight describes the breadth of building blocks now known to be accepted by the ribosome initiation machinery, from subtle methionine analogues to large exotic non-proteinogenic structures. We outline the key methodological developments that have enabled these discoveries, including the exploitation of methionyl-tRNA synthetase promiscuity, synthetase and tRNA engineering, and the utilization of artificial tRNA-loading ribozymes, flexizymes. Using these methods, the number and diversity of validated initiation building blocks is rapidly expanding permitting the use of the ribosome to synthesize ever more artificial polymers in search of new functional molecules.Keywords
Funding Information
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency
- Japan Agency for Medical Research and Development
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