Issue 31, 2020

Initiating ribosomal peptide synthesis with exotic building blocks

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.

Graphical abstract: Initiating ribosomal peptide synthesis with exotic building blocks

Article information

Article type
Highlight
Submitted
19 Feb 2020
Accepted
26 Mar 2020
First published
27 Mar 2020

Chem. Commun., 2020,56, 4265-4272

Author version available

Initiating ribosomal peptide synthesis with exotic building blocks

C. Tsiamantas, J. M. Rogers and H. Suga, Chem. Commun., 2020, 56, 4265 DOI: 10.1039/D0CC01291B

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