Genome-based bioprospecting of microbes for new therapeutics

Bioprospecting of natural sources for new medicines has a long and successful history, exemplified by the fact that over 50% of all drugs currently on the market are either derived from or inspired by natural products. However, development of new natural product-based therapeutics has been on the decline over the past 20 years, mainly owing to frequent re-discovery of already known compounds coupled with high costs for screening, characterization and development. With the onset of the genomic era allowing rapid sequencing and analysis of bacterial and fungal genomes, it became evident that these organisms possess ‘hidden treasures’ in the form of gene clusters potentially governing biosynthesis of novel biologically active compounds. This review highlights current progress in mining for and expression of these gene clusters, which may revolutionize the drug discovery pipelines in the near future.

Graphical abstract.Figure optionsDownload full-size imageDownload high-quality image (124 K)Download as PowerPoint slideHighlights► Microbial genomes contain multiple clusters for biosynthesis of chemically diverse compounds. ► Most of such genes remain silent, preventing the respective compounds from being discovered. ► Silent gene clusters can be activated and/or heterologously expressed. ► New microbial hosts and tools are needed to make the abovementioned process efficient. ► Synthetic biology will play a major role in the genome-based drug discovery.