Figure 2.

Features of RiPP pathways that enables combinatorial chemistry: 1) core peptide hypervariability (represented by variation in color of the core sequences), which allows to diversify the RiPP pathway products by simple mutations in the core sequence only; 2) broad-substrate pathways, which requires the respective PTM enzymes (shown in blue and green shapes corresponding to distinct PTMs) to be promiscuous enabling them to accept the diversity in the core substrate; 3) recognition sequences (shaded in blue and green boxes along with their respective PTM enzymes), which provide docking sites for these promiscuous enzymes, thus preserving chemistry, despite the susbtrate diversity; 4) pathway modularity, wherein certain units of the pathway act as modules that can be interchanged with other distinct pathways further diversifying PTM chemistry. For instance, recognition sequences from one pathway can be interchanged with PTM enzymes from another (represented by differently colored PTM enzymes deviant from the original) to generate new modifications (shown by stars) in the same core sequence.