CylA is a sequence-specific protease involved in toxin biosynthesis

Weixin Tang, Silvia C. Bobeica, Li Wang, Wilfred A. van der Donk

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)537-549
Number of pages13
JournalJournal of Industrial Microbiology and Biotechnology
Issue number3-4
StatePublished - Mar 29 2019


  • Lanthipeptides
  • Lantibiotics
  • Leader peptide
  • Natural products
  • Peptidase
  • RiPPs

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'CylA is a sequence-specific protease involved in toxin biosynthesis'. Together they form a unique fingerprint.

Cite this