Hohsaka Takahiro, Sisido Masahiko
Department of Bioscience and Biotechnology, Okayama University, 3-1-1 Tsushimanaka, 700-8530, Okayama, Japan.
Curr Opin Chem Biol. 2002 Dec;6(6):809-15. doi: 10.1016/s1367-5931(02)00376-9.
Chemical and biological diversity of protein structures and functions can be widely expanded by position-specific incorporation of non-natural amino acids carrying a variety of specialty side groups. After the pioneering works of Schultz's group and Chamberlin's group in 1989, noticeable progress has been made in expanding types of amino acids, in finding novel methods of tRNA aminoacylation and in extending genetic codes for directing the positions. Aminoacylation of tRNA with non-natural amino acids has been achieved by directed evolution of aminoacyl-tRNA synthetases or some ribozymes. Codons have been extended to include four-base codons or non-natural base pairs. Multiple incorporation of different non-natural amino acids has been achieved by the use of a different four-base codon for each tRNA. The combination of these novel techniques has opened the possibility of synthesising non-natural mutant proteins in living cells.
通过位点特异性掺入带有各种特殊侧链基团的非天然氨基酸，蛋白质结构和功能的化学及生物学多样性能够得到广泛扩展。1989年舒尔茨团队和钱伯林团队开展开创性工作之后，在扩展氨基酸种类、寻找tRNA氨基酰化新方法以及扩展用于指导氨基酸位置的遗传密码方面均取得了显著进展。通过氨基酰-tRNA合成酶或某些核酶的定向进化，已实现用非天然氨基酸对tRNA进行氨基酰化。密码子已扩展至包括四碱基密码子或非天然碱基对。通过对每个tRNA使用不同的四碱基密码子，已实现多种不同非天然氨基酸的掺入。这些新技术的结合为在活细胞中合成非天然突变蛋白开辟了可能性。
