Engineering of RiPP pathways for the production of artificial peptides bearing various non-proteinogenic structures

Peptides bearing non-proteinogenic structures characteristic of natural products have great potential as leads of pharmaceuticals. In the biosynthetic pathways of ribosomally synthesized and post-translationally modified peptides (RiPPs), the non-proteinogenic structures are generated by enzymatic structural modification on precursor peptides encoded in genetic information. The plasticity of this pathway, in which alterations of the precursor genes directly resulted in variation of the products by the process of modularly functioning enzymes, have greatly facilitated both in vivo and in vitro engineering of the pathways. Here, we review several examples of the synthesis of artificial peptides having non-proteinogenic structures by genetic engineering of RiPP pathways.