The biosynthesis and evolution of non-ribosomal peptides from hepatotoxic cyanobacteria (Academy of Finland)

Cyanobacteria make a broad range of small linear and cyclic peptides with enzyme inhibiting activities. Microcystins are produced by distantly related genera of cyanobacteria and are the end-products of a secondary metabolic pathway comprised of polyketide synthases and non-ribosomal peptide synthetases. The natural function of microcystins is uncertain but it has been suggested that they act as part of an elaborate chemical defense mechanism. They are potent natural toxins that have received a lot of attention in both the scientific literature and popular press. However, a comprehensive understanding of how and why these peptides are produced is lacking. In this study I compared the Anabaena sp. 90 unannotated genome with published annotated genomes and peptide synthetase gene clusters. I used a comparative approach to describing the genes encoding the non-ribosomal synthetase, polyketide synthase, ABC transporter, phosphopantetheinyl transferase and tailoring enzyme directly involved in the synthesis and efflux of these peptides. I undertook a phylogenetic study to unravel the evolutionary relationships between microcystins and the structurally related peptide nostophycin as well as other non-ribosomally produced peptides from a diverse selection of cyanobacteria. This study yielded information on how the production of these peptides is integrated into the genome of cyanobacteria and provided valuable insights into the origin of microcystins, their evolution and their function in the natural environment.

This project was a postdoctoral research grant from the Academy of Finland and lead to 12 publications in international peer reviewed scientific journals.