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

Abstract

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 in this paper we devised 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. 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.

Authors:
ORCiD logo [1];  [2];  [3];  [3]; ORCiD logo [4]; ORCiD logo [5]; ORCiD logo [6]
  1. Univ. of Illinois, Urbana-Champaign, IL (United States). Carl R. Woese Inst. for Genomic Biology
  2. Univ. of Illinois, Urbana-Champaign, IL (United States). Dept. of Biochemistry
  3. Univ. of Illinois, Urbana-Champaign, IL (United States). Dept. of Chemistry
  4. Univ. of Illinois, Urbana-Champaign, IL (United States). Carl R. Woese Inst. for Genomic Biology, and Dept. of Chemistry, and Beckman Inst. for Advanced Science and Technology
  5. Univ. of Illinois, Urbana-Champaign, IL (United States). Carl R. Woese Inst. for Genomic Biology, and Dept. of Chemistry, and Howard Hughes Medical Inst.
  6. Univ. of Illinois, Urbana-Champaign, IL (United States). Carl R. Woese Inst. for Genomic Biology, and Dept. of Biochemistry, Dept. of Chemistry, Dept. of Chemical and Biomolecular Engineering, and Dept. of Bioengineering
Publication Date:
Research Org.:
Univ. of Illinois, Champaign, IL (United States). Center for Advanced Bioenergy and Bioproducts Innovation (CABBI)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1471403
Grant/Contract Number:  
SC0018420
Resource Type:
Accepted Manuscript
Journal Name:
Journal of the American Chemical Society
Additional Journal Information:
Journal Volume: 140; Journal Issue: 38; Journal ID: ISSN 0002-7863
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Si, Tong, Tian, Qiqi, Min, Yuhao, Zhang, Linzixuan, Sweedler, Jonathan V., van der Donk, Wilfred A., and Zhao, Huimin. Rapid Screening of Lanthipeptide Analogs via In-Colony Removal of Leader Peptides in Escherichia coli. United States: N. p., 2018. Web. doi:10.1021/jacs.8b05544.
Si, Tong, Tian, Qiqi, Min, Yuhao, Zhang, Linzixuan, Sweedler, Jonathan V., van der Donk, Wilfred A., & Zhao, Huimin. Rapid Screening of Lanthipeptide Analogs via In-Colony Removal of Leader Peptides in Escherichia coli. United States. doi:10.1021/jacs.8b05544.
Si, Tong, Tian, Qiqi, Min, Yuhao, Zhang, Linzixuan, Sweedler, Jonathan V., van der Donk, Wilfred A., and Zhao, Huimin. Wed . "Rapid Screening of Lanthipeptide Analogs via In-Colony Removal of Leader Peptides in Escherichia coli". United States. doi:10.1021/jacs.8b05544. https://www.osti.gov/servlets/purl/1471403.
@article{osti_1471403,
title = {Rapid Screening of Lanthipeptide Analogs via In-Colony Removal of Leader Peptides in Escherichia coli},
author = {Si, Tong and Tian, Qiqi and Min, Yuhao and Zhang, Linzixuan and Sweedler, Jonathan V. and van der Donk, Wilfred A. and Zhao, Huimin},
abstractNote = {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 in this paper we devised 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. 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.},
doi = {10.1021/jacs.8b05544},
journal = {Journal of the American Chemical Society},
number = 38,
volume = 140,
place = {United States},
year = {2018},
month = {9}
}

Journal Article:
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