Expanding the Structural Diversity of Protein Building Blocks with Noncanonical Amino Acids Biosynthesized from Aromatic Thiols
Expanding the Structural Diversity of Protein Building Blocks with Noncanonical Amino Acids Biosynthesized from Aromatic Thiols
复制标题
利用芳香硫醇生物合成的非规范氨基酸扩大蛋白质构建模块的结构多样性
DOI：
10.1002/anie.202014540
复制
发表时间：
2021-02
期刊：
影响因子：
--
通讯作者：
Liu Tao
中科院分区：
文献类型：
--
作者：
Wang Yong;Chen Xiaoxu;Cai Wenkang;Tan Linzhi;Yu Yutong;Han Boyang;Li Yuxuan;Xie Yuanzhe;Su Yeyu;Luo Xiaozhou;Liu Tao
将结构新颖的非规范氨基酸（ncAAs）掺入蛋白质中对于科学和生物医学应用都是有价值的。为了扩大可用的ncAAs的结构多样性，并减少化学合成它们的负担，我们已经开发了一种通用的和简单的生物合成方法，用于通过用经济的市售或合成可获得的芳族硫醇喂养细胞将新型ncAAs遗传编码成重组蛋白。我们证明，通过劫持半胱氨酸生物合成酶，可以从这些简单的小分子前体生物合成近50种具有不同结构的ncAA，并且随后可以通过扩展的遗传密码将所得的ncAA并入蛋白质中。此外，我们证明，生物正交反应基团，如芳香族叠氮化物和芳香族酮，可以纳入绿色荧光蛋白或治疗抗体的高产率，允许随后的化学缀合。
Incorporation of structurally novel noncanonical amino acids (ncAAs) into proteins is valuable for both scientific and biomedical applications. To expand the structural diversity of available ncAAs and to reduce the burden of chemically synthesizing them, we have developed a general and simple biosynthetic method for genetically encoding novel ncAAs into recombinant proteins by feeding cells with economical commercially available or synthetically accessible aromatic thiols. We demonstrate that nearly 50 ncAAs with a diverse array of structures can be biosynthesized from these simple small‐molecule precursors by hijacking the cysteine biosynthetic enzymes, and the resulting ncAAs can subsequently be incorporated into proteins via an expanded genetic code. Moreover, we demonstrate that bioorthogonal reactive groups such as aromatic azides and aromatic ketones can be incorporated into green fluorescent protein or a therapeutic antibody with high yields, allowing for subsequent chemical conjugation.
登录
查看更多内容
DOI：
10.3390/molecules19011004
发表时间：
2014-01-15
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Ma Y;Biava H;Contestabile R;Budisa N;di Salvo ML
通讯作者：
di Salvo ML
影响因子：
48
作者：
Zhang MS;Brunner SF;Huguenin-Dezot N;Liang AD;Schmied WH;Rogerson DT;Chin JW
通讯作者：
Chin JW
影响因子：
15
作者：
Mehl, RA;Anderson, JC;Schultz, PG
通讯作者：
Schultz, PG
影响因子：
--
作者：
Lin Xia;Ming-jie Han;Lu Zhou;Aiping Huang;Zhaoya Yang;Tianyuan Wang;Fa-hui Li;Lu Yu;C. Tian;Zhongsheng Zang;Qing‐Zheng Yang;Chenli Liu;Wenxu Hong;Yi Lu;L. Alfonta;Jiangyun Wang
通讯作者：
Lin Xia;Ming-jie Han;Lu Zhou;Aiping Huang;Zhaoya Yang;Tianyuan Wang;Fa-hui Li;Lu Yu;C. Tian;Zhongsheng Zang;Qing‐Zheng Yang;Chenli Liu;Wenxu Hong;Yi Lu;L. Alfonta;Jiangyun Wang
影响因子：
6.1
作者：
Liu, Han;Hou, Yehua;Li, Zhimin
通讯作者：
Li, Zhimin