Rapid Screening of Lanthipeptide Analogs via In-Colony Removal of Leader Peptides in Escherichia coli.

Rapid Screening of Lanthipeptide Analogs via In-Colony Removal of Leader Peptides in Escherichia coli.
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通过菌落内去除大肠杆菌中的前导肽快速筛选兰硫肽类似物。

DOI:
10.1021/jacs.8b05544
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发表时间:
2018
影响因子:
15
通讯作者:
Zhao,Huimin
Zhao,Huimin
中科院分区:
化学1区
文献类型:
--
作者:
Si,Tong;Tian,Qiqi;Min,Yuhao;Zhang,Linzixuan;Sweedler,JonathanV;vanderDonk,WilfredA;Zhao,Huimin

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Most native producers of ribosomally synthesized and post-translationally modified peptides (RiPPs) utilize N-terminal leader peptides to avoid potential cytotoxicity of mature products to the hosts. Unfortunately, the native machinery of leader peptide removal is often difficult to reconstitute in heterologous hosts. Here we devised a general method to produce bioactive lanthipeptides, a major class of RiPP molecules, inEscherichia colicolonies using synthetic biology principles, where leader peptide removal is programmed temporally by protease compartmentalization and inducible cell autolysis. We demonstrated the method for producing two lantibiotics, haloduracin and lacticin 481, and performed analog screening for haloduracin. This method enables facile, high throughput discovery, characterization, and engineering of RiPPs.
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