Expansion of the Borosin RiPP Family of α-N-Methylated Peptide Natural Products
In a recent issue of the Journal of the American Chemical Society, the Künzler group (IMB) expands on the recently discovered family of borosins, ribosomally synthesized and posttranslationally modified peptide (RiPP) natural products featuring α-N-methylation.
The oral availability of peptide therapeutics depends on their proteolytic stability and membrane permeability. α-N-methylation is a modification that can provide both properties and is mainly found on non-ribosomal peptides in nature. In 2017, a set of α-N-methylated fungal peptide natural products, omphalotins, was discovered as founding members of a novel family of ribosomally synthesized and posttranslationally modified peptides (RiPPs) referred to as borosins. Here we shed light on the structural diversity of the borosins by identifying of 50 putative peptide precursors in a variety of ascomycete and basidiomycete fungi and functionally validating nearly a dozen of them. Significant differences in precursor size, architecture, and core peptide properties subdivide this RiPP family into three discrete types. Using targeted genomics, we also identify the antineoplastic gymnopeptides as members of this RiPP family. This work highlights the metabolic potential of fungi for peptide natural products.
Link to the paper in the external page Journal of the American Chemical Society.