Ribosomal Elongation of Aminobenzoic Acid Derivatives

2-Aminobenzoic acid and heterocyclic amino acids are aromatic homologues of β-amino acids, but their chemical properties are quite distinct. Because of the poor nucleophilicity of the amino group conjugated with the aromatic ring, no literature reports of their successful ribosomal elongation in nascent peptide chains have appeared to date. Here we report for the first time their incorporation in nascent peptide chains by means of a reconstituted translation system in which a designer tRNAPro1E2 capable of recruiting the elongation factors EF-Tu and EF-P was charged with their derivatives and the corresponding peptides were successfully expressed. We also demonstrate the expression of macrocyclic peptides containing exotic amino acids, including aminobenzoic acid derivatives.

邻氨基苯甲酸（2-Aminobenzoic acid）与杂环氨基酸均为β-氨基酸（β-amino acids）的芳香同系物，但二者化学性质差异显著。因氨基与芳香环共轭导致亲核性较弱，迄今为止尚无文献报道其可在新生肽链（nascent peptide chains）中完成核糖体延伸（ribosomal elongation）。本研究首次借助重建翻译系统（reconstituted translation system）实现了此类氨基酸在新生肽链中的掺入：我们将可招募延伸因子EF-Tu与EF-P的定制化tRNAPro1E2，用目标氨基酸衍生物完成氨酰化负载，随后成功表达出对应的肽链。此外，本研究还证实了包含邻氨基苯甲酸衍生物等非常规氨基酸组分的大环肽（macrocyclic peptides）的表达可行性。