Synthesis of a Truncated Microcystin Tetrapeptide Molecule from a Partial Mcy Gene Cluster in Microcystis Cultures and Blooms

Article (Faculty180)

cited authors

  • Yancey, Colleen E; Hart, Lauren; Lad, Apurva Chandrakan C; Birbeck, Johnna A; Song, Siliang; Mohamed, Osama G; Fribley, Andrew M; Haller, Steven T; Tripathi, Ashootosh; Kennedy, David J; Westrick, Judy A; Sherman, David H; Dick, Gregory J

description

  • <p>spp. threaten freshwater ecosystems through the proliferation of cyanobacterial harmful algal blooms (cyanoHABs) and production of the hepatotoxin, microcystin. While microcystin and its biosynthesis pathway, encoded by the genes, have been well studied for over 50 years, a recent study found that populations in western Lake Erie contain a transcriptionally active partial operon, in which the A2 domain of and are present but the genes are absent. Here, we investigate the potential biosynthetic products and the evolutionary history of this partial operon. Our results reveal two candidate tetrapeptide constructs, with an X variable position, to be produced by strains with the partial operon. The partial operon appears necessary and sufficient for tetrapeptide biosynthesis and likely evolved from a single ancestor hundreds to tens of thousands of years ago. Bioactivity screens using Hep3B cells indicate a mild elevation of some markers of hepatotoxicity and inflammation, suggesting the need to further assess the effects of these novel secondary metabolites on freshwater ecosystems and public health. The need to assess these effects is even more pressing given the detection of tetrapeptides in both culture and western Lake Erie, which is a vital source of fresh water. Results from this study emphasize previous findings in which novel bacterial secondary metabolites may be derived from the molecular evolution of existing biosynthetic machinery under different environmental forcings.</p>

authors

publication date

  • 2024

published in

start page

  • 19936

end page

  • 19947

volume

  • 58