Pseudokinases can catalyse peptide cyclization through thioether crosslinking

Nature Chemistry, Published online: 02 October 2025; doi:10.1038/s41557-025-01954-1

Pseudokinases are non-canonical protein-kinase-like proteins deficient in kinase activity, few of which have enzymatic activity that differs from phosphorylation. Now a pseudokinase-enabled cyclization activity for the biosynthesis of ribosomally synthesized and post-translationally modified peptides has been observed. Here pseudokinases can catalyse a Michael addition for (ene)thioether crosslinking through a sandwich-like substrate-assisted process.

​Nature Chemistry, Published online: 02 October 2025; doi:10.1038/s41557-025-01954-1Pseudokinases are non-canonical protein-kinase-like proteins deficient in kinase activity, few of which have enzymatic activity that differs from phosphorylation. Now a pseudokinase-enabled cyclization activity for the biosynthesis of ribosomally synthesized and post-translationally modified peptides has been observed. Here pseudokinases can catalyse a Michael addition for (ene)thioether crosslinking through a sandwich-like substrate-assisted process. Read More

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