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.
Published in JACS, researchers from the groups of Huimin Zhao and Wilfred van der Donk, both at the University of Illinois, describe a general method to produce bioactive lanthipeptides, a major class of RiPP molecules, in Escherichia coli colonies using synthetic biology principles, where leader peptide removal is programmed temporally by protease compartmentalization and inducible cell autolysis.
The collaborion demonstrates 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.
Rapid Screening of Lanthipeptide Analogs via In-Colony Removal of Leader Peptides in Escherichia coli
Tong Si, Qiqi Tian, Yuhao Min, Linzixuan Zhang, Jonathan V. Sweedler, Wilfred A. van der Donk, and Huimin Zhao
J. Am. Chem. Soc., 2018, 140 (38), pp 118840-11888