Dissecting Biosynthesis of Natural Products Toward Drug Discovery

Abstract

Microorganisms have developed diverse metabolic systems for enduring in a competitive society of nature. While some microbial species threaten human beings as the cause of infectious disease, there are many examples how people have utilized microbial potential to produce fermented foods, beverages, and pharmaceuticals, all of which are indispensable for maintaining the quality of human life. A significant factor that triggers biological phenotypes in the recipient is microbe-producing small organic molecules, also known as natural products. In the current post-genomic era, many of the specialized biosynthetic pathways of natural products have been identified and linked to their biosynthesis genes, enabling us to design, harness, and create the pathway to obtain more valuable substances. In this chapter, we initially introduce the biosynthesis of aspirochlorine, a potent antifungal agent produced by a beneficial fungus, Aspergillus oryzae, which has been utilized in East Asia for brewing fermented products. Then, we focus on potential drug candidates, fumagillin and pseurotins, produced by a human-pathogenic fungus Aspergillus fumigatus. As toxin and medicine are two sides of the same coin, deciphering and manipulating the biosynthetic pathways of bioactive natural products will facilitate the discovery of untapped therapeutics.