Strategies for the Discovery of New Natural Products by Genome Mining

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Abstract
New drugs from silent gene clusters: Analysis of genome sequence data has identified numerous “cryptic” gene clusters encoding novel natural product biosynthetic assembly lines; this suggests that many new bioactive metabolites remain to be discovered, even in extensively investigated organisms. Several related and complementary strategies for identifying the products of these clusters have emerged recently and revitalized the search for novel bioactive natural products. magnified image Natural products have a very broad spectrum of applications. Many natural products are used clinically as antibacterial, antifungal, antiparasitic, anticancer and immunosuppressive agents and are therefore of utmost importance for our society. When in the 1940s the golden age of antibiotics was ushered in, a “gold rush fever” of natural product discovery in the pharmaceutical industry ensued for many decades. However, the traditional process of discovering new bioactive natural products is generally long and laborious, and known natural products are frequently rediscovered. A mass‐withdrawal of pharmaceutical companies from new natural product discovery and natural products research has thus occurred in recent years. In this article, the concept of genome mining for novel natural product discovery, which promises to provide a myriad of new bioactive natural compounds, is summarized and discussed. Genome mining for new natural product discovery exploits the huge and constantly increasing quantity of DNA sequence data from a wide variety of organisms that is accumulating in publicly accessible databases. Genes encoding enzymes likely to be involved in natural product biosynthesis can be readily located in sequenced genomes by use of computational sequence comparison tools. This information can be exploited in a variety of ways in the search for new bioactive natural products.