Targeting Bacterial Genomes for Natural Product Discovery. (January 2020)

• Record Type: Journal Article
• Authors: Kalkreuter, Edward; Pan, Guohui; Cepeda, Alexis J.; Shen, Ben
• Is Part Of: Trends in pharmacological sciences. Volume 41:Number 1(2020)
• Page Start: 13
• Page End: 26
• Publication Date: 2020-01
• Subjects: genome mining -- natural products -- drug discovery -- biosynthetic gene clusters -- polyketides -- nonribosomal peptides; Pharmacology -- Periodicals; Pharmacology -- trends -- Periodicals; Pharmacologie -- Périodiques; Pharmacology; Electronic journals; Periodicals; 615.1
• DOI: 10.1016/j.tips.2019.11.002
• Languages: English
• ISSNs: 0165-6147

Abstract

Abstract : Bacterial natural products (NPs) and their analogs constitute more than half of the new small molecule drugs developed over the past few decades. Despite this success, interest in natural products from major pharmaceutical companies has decreased even as genomics has uncovered the large number of biosynthetic gene clusters (BGCs) that encode for novel natural products. To date, there is still a lack of universal strategies and enabling technologies to discover natural products at scale and speed. This review highlights several of the opportunities provided by genome sequencing and bioinformatics, challenges associated with translating genomes into natural products, and examples of successful strain prioritization and BGC activation strategies that have been used in the genomic era for natural product discovery from cultivatable bacteria. Highlights: Genomics has revealed the largely untapped source of bacterial natural products and the associated opportunities for discovering novel natural products, which serve as an unprecedented source for new drugs. It is critically important to intelligently prioritize which biosynthetic gene clusters to target for discovery and development out of the millions of possibilities now afforded by genomics. Bioinformatics tools have advanced to the point that biosynthetic gene clusters can be targeted for novelty in product structure or function, although progress is still needed before this can be considered a universal strategy. Most bacterial biosynthetic gene clusters do not produce natural products under typical laboratory culturing conditions, but many strategies have been developed for the activation of these gene clusters.