Bartolosides E-K from a Marine Coccoid Cyanobacterium

Abstract

The glycosylated and halogenated dialkylresorcinol (DAR) compounds bartolosides A-D (1-4) were recently discovered from marine cyanobacteria and represent a novel family of glycolipids, encoded by the brt biosynthetic gene cluster. Here, we report the isolation and NMR- and MS-based structure elucidation of monoglycosylated bartolosides E-K (5-11), obtained from Synechocystis salina LEGE 06099, a strain closely related to the cyanobacterium that produces the diglycosylated 2-4. In addition, a genome region containing orthologues of brt genes was identified in this cyanobacterium. Interestingly, the major bartoloside in S. salina LEGE 06099 was 1 (above 0.5% dry wt), originally isolated from the phylogenetically distant filamentous cyanobacterium Nodosilinea sp. LEGE 06102. Compounds 5-11 are analogues of 1, with different alkyl chain lengths or halogenation patterns. Their structures and the organization of the brt genes suggest that the DAR-forming ketosynthase BrtD can generate structural diversity by accepting fatty acyl-derived substrates of varying length. Compound 9 features a rare midchain gem-dichloro moiety, indicating that the putative halogenase BrtJ is able to act twice on the same midchain carbon.