Ribosomal peptide natural products: bridging the ribosomal and nonribosomal worlds

Abstract

Ribosomally synthesized bacterial natural products rival the nonribosomal peptides in their structural and functional diversity. The last decade has seen substantial progress in the identification and characterization of biosynthetic pathways leading to ribosomal peptide natural products with new and unusual structural motifs. In some of these cases, the motifs are similar to those found in nonribosomal peptides, and many are constructed by convergent or even paralogous enzymes. Here, we summarize the major structural and biosynthetic categories of ribosomally synthesized bacterial natural products and, where applicable, compare them to their homologs from nonribosomal biosynthesis.

Figure 1. Examples of structurally diverse post-translationally modified RPs from bacteria

Figure 2. Generic biosynthetic route to bacterial RPs

In bacteria, a gene for a precursor peptide (orange) is often clustered with its modifying enzymes. The precursor peptide is translated, then posttranslationally modified by the encoded enzymes. Commonly, posttranslational modifications include both side chain modification and main chain modification such as proteolysis to generate the mature natural product.

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