Monday, August 12, 2013
Pavilion (Sheraton San Diego)
Marine natural products and their derivatives possess a wide rage of promising bioactivities. However, generally the amounts of these bioactive materials that can be isolated from Nature are limited. Moreover, cutlivation and genetic manipulation of source organisms or total chemical synthesis of structurally complex metabolites are difficult. Therefore, a reliable method must be developed for the increased supplies and structural diversification of these marine compounds to harness their therapeutic potential. Ultimately, establishement of a heterologous expression platform for the biosynthetic gene clusters derived from marine invertebrates and bacteria in more amenable bacterial hosts could provide a microbial cell factory as a sustainable source of valuable marine compounds and as a toolbox for combinatorial biosynthesis of related analogs. In this study, heterologous expression of the barbamide biosynthetic gene cluster from the marine cyanobacterium Moorea producens in the terrestrial actinobacterium Streptomyces venezuelae, resulted in the production of a new barbamide congener ‘4-O-demethylbarbamide’ which shows 10-fold higher molluscicidal activity compared to barbamide, demonstrating the potential of this approach for the large-scale production and investigating the biosynthesis of complex marine natural products.