Major gene‐regulatory mechanisms operating in ribosomally synthesized and post‐translationally modified peptide (RiPP) biosynthesis

Summary Post‐translationally modified peptides commonly display antimicrobial activity, but can also aid the development of bacterial colonies, giving a competitive advantage in the ecological niche. The production of post‐translationally modified peptides by bacteria is a complex and energetically costly process that is strictly orchestrated in the cell. The onset of peptide production is linked to the different enzymes that take part during maturation, the transporters and the immunity determinants (if required). Thus, the population can make optimal use of available resources and obtain the benefits of production at an advantageous moment during growth, avoiding toxicity to itself. The timing and level of expression of the different operons is controlled by diverse (complex) regulatory pathways in response to environmental changes, stress or master regulators during specific growth transition phases. In this review, we highlight the basic principles and mechanisms of regulation of expression of post‐translationally modified peptides and the relationship with the overall culture developmental processes and/or cellular differentiation. We also discuss the biotechnological consequences derived from the understanding of regulatory networks involved in the biosynthesis of these natural products. The biosynthesis of ribosomally synthesized and post‐translationally modified peptides (RiPPs) is a highly complex process which involves the activity of several modification enzymes, transporters and immunity determinants. The ideal time point of the expression itself is crucial for the cell and has to be tightly regulated. This MicroReview presents and explains the most common regulatory mechanisms of RiPP biosynthesis and groups them according to their mode of action.