Ecology and evolution of lanthipeptides in marine picocyanobacteria

Abstract

Microbial secondary metabolites are among the most structurally and functionally complex molecules in nature. Lanthipeptides are ribosomally derived peptide secondary metabolites that undergo extensive post-translational modification. Most lanthipeptides are bactericidal but they are also known to act as signaling molecules or morphogenetic peptides, nevertheless the function of many lanthipeptides remains unknown. Prochlorosins are a diverse group of lanthipeptides produced by strains of the ubiquitous marine picocyanobacteria Prochlorococcus and Synechococcus. Unlike other lanthipeptide-producing bacteria, picocyanobacteria utilize an unprecedented mechanism of catalytic promiscuity for the production multiple structurally diverse lanthipeptides using a single biosynthetic enzyme. Also unprecedented is the production of lanthipeptides by single celled, planktonic gram-negative bacteria in a dilute nutrient-limited habitat, which suggests that they may have an unconventional biological function. The overarching goal of this thesis is to further our understanding of the ecology and evolution of the prochlorosins, and provide insights into their biological role in the marine environment. Here, we demonstrate that the prochlorosin genes are widespread in the ocean and that globally distributed populations of marine picocyanobacteria have the genetic potential of producing thousands of different lanthipeptide structures. The diversity of prochlorosin structures provides an interesting model to study the evolutionary forces that drive the creation of new lanthipeptide structures. We present evidence that there is a unique evolutionary interplay between the components of prochlorosin biosynthesis pathway; while the peptide substrates independently expand and diversify within the genome, the catalytically promiscuous biosynthetic enzyme evolves under a strong purifying selection that maintains its substrate tolerant state. This relationship indicates that the lanthipeptide production trait in marine picocyanobacteria might find its evolutionary advantage in the plasticity of the production of multiple cyclic peptides with diverse ring topologies. The remarkable diversity of prochlorosins poses many questions regarding their biological role in the marine environment. In laboratory experiments, we explore of some of the potential bioactivity of the prochlorosins, namely their potential as signaling molecules, antimicrobials and nutrient sources. The results from this exploration open new perspectives for the role of the lanthipeptides in the natural environment - more specifically the oligotrophic ocean.