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Put a Bow on It: Knotted Antibiotics Take Center Stage

By Stephanie Tan, Gaelen Moore and Justin Nodwell


Ribosomally-synthesized and post-translationally modified peptides (RiPPs) are a large class of natural products produced across all domains of life. The lasso peptides, a subclass of RiPPs with a lasso-like structure, are structurally and functionally unique compared to other known peptide antibiotics in that the linear peptide is literally &ldquo;tied in a knot&rdquo; during its post-translational maturation. This underexplored class of peptides brings chemical diversity and unique modes of action to the antibiotic space. To date, eight different lasso peptides have been shown to target three known molecular machines: RNA polymerase, the lipid II precursor in peptidoglycan biosynthesis, and the ClpC<sub>1</sub> subunit of the Clp protease involved in protein homeostasis. Here, we discuss the current knowledge on lasso peptide biosynthesis as well as their antibiotic activity, molecular targets, and mechanisms of action

Year: 2019
DOI identifier: 10.3390/antibiotics8030117
OAI identifier: oai:localhost:1807/96369
Provided by: TSpace Repository
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