Natural products discovery and potential for new antibiotics.

Microbial natural products have been one of the most important sources for the discovery of potential new antibiotics. However, the decline in the number of new chemical scaffolds discovered and the rediscovery problem of old known molecules has become a limitation for discovery programs developed by an industry confronted by a lack of incentives and a broken economic model. In contrast, the emergence of multidrug resistance in key pathogens has continued to progress and this issue is compounded by a lack of new antibiotics in development to address most of the difficult to treat infections. Advances in genome mining have confirmed the richness of biosynthetic gene clusters (BGCs) in the majority of microbial sources, and this suggests that an untapped chemical diversity is waiting to be discovered. The development of new genome engineering and synthetic biology tools, and the implementation of comparative omic approaches is fostering the development of new integrated culture-based strategies and genomic-driven approaches aimed at delivering new chemical classes of antibiotics.