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Co-opting the bacterial lipoprotein pathway for the biosynthesis of lipidated macrocyclic peptides - PubMed

4 hours ago
  • #Macrocyclic Peptides
  • #RiPPs
  • #Bacterial Lipoprotein Pathway
  • The study co-opts the bacterial lipoprotein pathway to synthesize lipidated macrocyclic peptides.
  • It focuses on RiPPs (ribosomally synthesized and posttranslationally modified peptides), which have diverse bioactivities.
  • Enzymes like ChrH catalyze complex modifications, creating structures like macrocycles and heterocycles.
  • Comparative genomics reveals structural diversity, including unmethylated macrocyclic forms and large C-terminally modified proteins.
  • Some precursors have signal peptides, directing them to the bacterial lipoprotein pathway for maturation.
  • This process adds a diacylglycerol (DAG) group to the N-terminal cysteine and acylates the amine.
  • These hybrids, termed DAG-RiPPs, are widespread across bacteria and may serve various biological roles.
  • The findings highlight a new maturation paradigm for membrane-bound RiPPs and support future bioengineering.