CylA is a sequence-specific protease involved in toxin biosynthesis

  • Weixin Tang
  • Silvia C. Bobeica
  • Li Wang
  • Wilfred A. van der DonkEmail author
Natural Products - Original Paper


CylA is a subtilisin-like protein belonging to a recently expanded serine protease family related to class II lanthipeptide biosynthesis. As a leader peptidase, CylA is responsible for maturation of the enterococcal cytolysin, a lantibiotic important for Enterococcus faecalis virulence. In vitro reconstitution of CylA reveals that it accepts both linear and modified cytolysin peptides with a preference for cyclized peptides. Further characterization indicates that CylA activates itself by removing its N-terminal 95 amino acids. CylA achieves sequence-specific traceless cleavage of non-cognate peptides even if they are post-translationally modified, which makes the peptidase a powerful tool for mining novel lanthipeptides by providing a general strategy for leader peptide removal. Knowledge about the substrate specificity of CylA may also facilitate the development of protease inhibitors targeting cytolysin biosynthesis as a potential therapeutic approach for enterococcal infections.


Natural products RiPPs Lanthipeptides Lantibiotics Leader peptide Peptidase 



This study was supported by the National Institutes of Health (R37 GM 058822 to W.A.V.).

Author contributions

WT and WAvdD designed the study. WT and SCB performed all experiments. WT, SCB, LW and WAvdD analyzed the data, and WT and WAvdD wrote the manuscript.

Compliance with ethical standards

Conflict of interests

The authors declare no competing financial interests.

Supplementary material

10295_2018_2110_MOESM1_ESM.pdf (1.8 mb)
Supplementary material 1 (PDF 1855 kb)


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Copyright information

© Society for Industrial Microbiology and Biotechnology 2018

Authors and Affiliations

  1. 1.Department of ChemistryHoward Hughes Medical Institute, University of Illinois at Urbana-ChampaignUrbanaUSA
  2. 2.Broad Institute of MIT and HarvardCambridgeUSA

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