Year: 2026
Type: article
Abstract: Serine proteases in ribosomally synthesized and post-translationally modified peptides (RiPPs) catalyze the cleavage on the precursor peptides in the biosynthesis of RiPP natural products. Here, we identified an uncharacterized serine protease WprP2 from Streptomyces venezuelae NPDC049867, encoded next to the radical S-adenosyl-L-methionine (SAM) enzyme WprB2 involved in the biosynthesis of cyclophane natural products. In vitro characterization of S9 protease WprP2 revealed that the precursor peptide WprA2 is uniformly cleaved. The cleavage activity of WprP2 has not been seen in any serine proteases and expands the S9 protease in RiPP biosynthesis. Ribosomally synthesized and post-translationally modified peptides (RiPPs) require precise proteolytic cleavage to generate bioactive natural products, yet the diversity of serine proteases involved remains underexplored. Here, the authors identify and characterize the serine protease WprP2 from Streptomyces venezuelae NPDC049867, revealing its unique cleavage activity on precursor peptides WprA2 involved in the biosynthesis of cyclophane RiPP natural products.
Source: Communications Chemistry
Institutions: Latvijas Organiskās Sintēzes Institūts, Fudan University
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,690
OpenAlex ID: W7126054790