Structure, Synthesis of Hierridin C and Discovery of Prevalent Alkylresorcinol Biosynthesis in Picocyanobacteria

Small, single-celled planktonic cyanobacteria are ubiquitous in the world’s oceans yet tend not to to be perceived as biosynthetically-prolific organisms. Here we report the isolation and structure elucidation of hierridin C, an antiplasmodial halogenated alkylresorcinol produced in very low amounts by the picocyanobacterium <i>Cyanobium</i>sp. LEGE 06113. We describe a simple, straightforward synthetic route to the scarcely-produced hierridins that relies on a key, highly regioselective halogenation step. In addition, we show that these compounds originate from a type III PKS pathway and that similar biosynthetic gene clusters are found in a variety of bacterial genomes, most notably those of the globally-distributed picocyanobacteria genera <i>Prochlorococcus</i>, <i>Cyanobium</i>and <i>Synechococcus</i>.