Initiating ribosomal peptide synthesis with exotic building blocks.,Chemical Communications

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Initiating ribosomal peptide synthesis with exotic building blocks.
Chemical Communications ( IF 4.3 ) Pub Date : 2020-04-08 , DOI: 10.1039/d0cc01291b
Christos Tsiamantas ₁ , Joseph M Rogers , Hiroaki Suga

Affiliation

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.

中文翻译：

用外来结构单元启动核糖体肽合成。

核糖体肽的合成几乎全部始于整个生活领域的氨基酸蛋氨酸。蛋氨酸引发的普遍性提出了一个问题。用其他氨基酸，蛋白质或其他氨基酸可以在多大程度上实现多肽合成？此重点介绍了从微小的蛋氨酸类似物到大型的非蛋白原性结构，现在已知已被核糖体起始机制接受的构件的广度。我们概述了促成这些发现的关键方法学发展，包括对甲硫氨酰-tRNA合成酶的滥交，合成酶和tRNA工程的利用，以及人工加载tRNA的核酶，自由酶的利用。使用这些方法，

更新日期：2020-04-16

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