CylA is a sequence-specific protease involved in toxin biosynthesis

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

Research output: Contribution to journalArticle

Abstract

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
Volume46
Issue number3-4
DOIs
StatePublished - Mar 29 2019

Fingerprint

Perforin
Biosynthesis
Peptide Hydrolases
Peptides
Subtilisin
Bacteriocins
Enterococcus faecalis
Serine Proteases
Protein Sorting Signals
Substrate Specificity
Protease Inhibitors
Virulence
Amino acids
Amino Acids
Substrates
Infection
Proteins
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

CylA is a sequence-specific protease involved in toxin biosynthesis. / Tang, Weixin; Bobeica, Silvia C.; Wang, Li; van der Donk, Wilfred Adrianus.

In: Journal of Industrial Microbiology and Biotechnology, Vol. 46, No. 3-4, 29.03.2019, p. 537-549.

Research output: Contribution to journalArticle

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