Natural Product Sciences in Modern Drug Discovery and Paths to the Future
Natural products with their specific structural features deliver chemical starting points in drug discovery to develop innovative therapies for diseases for which no or only unsatisfactory treatments exist. The evolved function of natural products in regulating physiological pathways in nature makes them to a biologically biased and complementary source of chemical probes to decipher novel modes of molecular interactions. As there is a high need for specific modulators of new targets, the access to novel natural product chemotypes and the understanding of their modulatory activities are gaining increasing attraction in today’s drug research. The fragmentation of natural products to generate new sp3-enriched chemicals expands the research toolbox in chemistry and chemical biology. Selected examples will illustrate how new natural products scaffolds and natural products-inspired synthetics are shuttles to a new biological space of therapeutic relevance.
The technological driving forces of Synthetic Biology, genome sequencing and DNA-synthesis, are changing the face of modern natural products research. Whole genome data of microorganisms reveals that encoding genes for natural products biosynthesis pathways, their corresponding resistance factors, and for nearby positioned metabolite pathways can form cooperative functional entities. These “co-localization signatures” prompt the investigation of potential biological synergisms of encoded metabolites or enable natural product-target pair analyses by comparative genomics.
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