Combinatorial Natural Products: From Cloning to Analysis

Abstract

Medicinal compounds from plants represent one of the largest and most diverse groups of plant secondary metabolites. The advent of advanced bioinformatics tools and modern genetic technology allowed for manipulation of biosynthetic pathways with the potential of generating novel chemical entities. First, public databases of secondary metabolite related enzymes were interrogated to identify relevant plant genes from vinca rosea (Catharanthus roseus) and other species. Genes of interest were tested after cloning by transfection into tobacco cell cultures using DNA viral vectors. The biosynthetic enzymes coded by these genes were over-expressed in the host. Automated solvent extraction procedure was employed to extract secondary metabolites from plant leaf tissues and transfected tobacco cell culture samples. The composition of the extracts was analyzed by state of the art bioanalytical methods such as high performance liquid chromatography and capillary electrophoresis to monitor changes in secondary metabolite patterns.

The future of plant drug discovery

“…These genes could be used for 'bioengineering' plant secondary metabolism, even when the pathways are unknown. Several foreign genes (as previously identified) might be inserted into a different plant species and used to modify existing products or create new ones [50] . Some of these methods have been used successfully for nutritional traits [51] , but pharmaceutical applications are relatively unexplored.…”