Ribosomal Elongation of Aminobenzoic Acid Derivatives
Ribosomal Elongation of Aminobenzoic Acid Derivatives
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DOI：
10.1021/jacs.0c05765
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发表时间：
2020-09-30
影响因子：
15
通讯作者：
Suga, Hiroaki
中科院分区：
文献类型：
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作者：
Katoh, Takayuki;Suga, Hiroaki
2-氨基苯甲酸和杂环氨基酸是β-氨基酸的芳香族同系物，但它们的化学性质却截然不同。由于与芳环缀合的氨基的亲核性差，迄今为止还没有文献报道它们在新生肽链中成功地延长核糖体。在这里，我们报告的第一次，他们的新生肽链的重组翻译系统，其中设计师tRNA（Pro 1 E2）能够招募的延伸因子EF-Tu和EF-P的重组翻译系统的方式纳入收费与他们的衍生物和相应的肽被成功表达。我们还展示了含有外来氨基酸的大环肽的表达，包括氨基苯甲酸衍生物。
2-Aminobenzoic acid and heterocyclic amino acids are aromatic homologues of beta-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 tRNA(Pro1E2) 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.