Unusual Sesquiterpenes from Streptomyces olindensis DAUFPE 5622

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2024-03, Vol.87 (3), p.491-500
• Main Authors: Chagas, Fernanda O., Garrido, Leandro M., Conti, Raphael, Borges, Ricardo M., Bielinski, Vincent A., Padilla, Gabriel, Pupo, Mônica T.
• Format: Article
• Language: English
• Subjects: biochemical pathways; biosynthesis; genes; glycosylation; hydrolysis; phosphates; sesquiterpenoids; Streptomyces
• ISSN: 0163-3864; 1520-6025; 1520-6025
• DOI: 10.1021/acs.jnatprod.3c00752

In nature, the vast majority of sesquiterpenes are produced by type I mechanisms, and glycosylated sesquiterpenes are rare in actinobacteria. Streptomyces olindensis DAUFPE 5622 produces the sesquiterpenes olindenones A–G, a new class of rearranged drimane sesquiterpenes. Olindenones B–D are oxygenated derivatives of olindenone A, while olindenones E–G are analogs glycosylated with dideoxysugars. 13C-isotope labeling studies demonstrated olindenone A biosynthesis occurs via the methylerythritol phosphate (MEP) pathway and suggested the rearrangement is only partially concerted. Based on the structures, one potential mechanism of olindenone A formation proceeds by cyclization of the linear terpenoid precursor, likely occurring via a terpene cyclase-mediated type II mechanism whereby the terminal alkene of the precursor is protonated, triggering carbocation-driven cyclization followed by rearrangement. Diphosphate hydrolysis may occur either before or after cyclization. Although a biosynthetic route is proposed, the terpene cyclase gene responsible for producing olindenones currently remains unidentified.