Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
Chembiochem. 2019 Jun 3;20(11):1357-1364. doi: 10.1002/cbic.201800733. Epub 2019 Mar 13.
Expanding the genetic code of organisms by incorporating noncanonical amino acids (ncAAs) into target proteins through the suppression of stop codons in vivo has profoundly impacted how we perform protein modification or detect proteins and their interaction partners in their native environment. Yet, with genetic code expansion strategies maturing over the past 15 years, new applications that make use-or indeed repurpose-these techniques are beginning to emerge. This Concept article highlights three of these developments: 1) The incorporation of ncAAs for the biosynthesis and selection of bioactive macrocyclic peptides with novel ring architectures, 2) synthetic biocontainment strategies based on the addiction of microorganisms to ncAAs, and 3) enzyme design strategies, in which ncAAs with unique functionalities enable the catalysis of new-to-nature reactions. Key advances in all three areas are presented and potential future applications discussed.
通过在体内抑制终止密码子将非规范氨基酸（ncAAs）掺入靶蛋白中，从而扩展生物体的遗传密码，这极大地改变了我们对蛋白质进行修饰或在其天然环境中检测蛋白质及其相互作用伙伴的方式。然而，随着遗传密码扩展策略在过去 15 年中的不断成熟，开始出现利用或重新利用这些技术的新应用。本文重点介绍了这三个方面的发展：1）利用 ncAAs 合成和选择具有新型环结构的生物活性大环肽；2）基于微生物对 ncAAs 的成瘾性的合成生物控制策略；3）酶设计策略，其中具有独特功能的 ncAAs 可实现新天然反应的催化。介绍了这三个领域的关键进展，并讨论了潜在的未来应用。
