Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA.
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India.
Chembiochem. 2020 May 15;21(10):1387-1396. doi: 10.1002/cbic.202000017. Epub 2020 Mar 2.
Genetic code expansion (GCE) has revolutionized the field of protein chemistry. Over the past several decades more than 150 different noncanonical amino acids (ncAAs) have been co-translationally installed into proteins within various host organisms. The vast majority of these ncAAs have been incorporated between the start and stop codons within an open reading frame. This requires that the ncAA be able to form a peptide bond at the α-amine, limiting the types of molecules that can be genetically encoded. In contrast, the α-amine of the initiating amino acid is not required for peptide bond formation. Therefore, including the initiator position in GCE allows for co-translational insertion of more diverse molecules that are modified, or completely lacking an α-amine. This review explores various methods which have been used to initiate protein synthesis with diverse molecules both in vitro and in vivo.
遗传密码扩展（GCE）彻底改变了蛋白质化学领域。在过去的几十年中，已经有超过 150 种不同的非天然氨基酸（ncAA）在各种宿主生物中被共翻译地掺入到蛋白质中。这些 ncAA 中的绝大多数是在开放阅读框中的起始密码子和终止密码子之间掺入的。这要求 ncAA 能够在α-氨基处形成肽键，从而限制了可以遗传编码的分子类型。相比之下，起始氨基酸的α-氨基不需要形成肽键。因此，在 GCE 中包括起始位置可以允许共翻译插入更多经过修饰或完全缺乏α-氨基的不同分子。本文综述了在体外和体内使用各种方法来起始具有不同分子的蛋白质合成的方法。
