Chapter 7 - Modern approaches for mining of novel compounds from the microbes

Abstract

After a few golden years of drug discovery, interest in microbial compounds dropped dramatically, primarily due to high rates of the re-discovery of natural compounds (NCs) and access to millions of synthetic compounds generated using combinatorial chemistry. Yet the fact remains that the success rate of druggable compounds remains much higher for NCs of microbial origin than for structures made by chemical synthesis. Recent technical advances in genome analysis and mass spectrometry now offer new opportunities to access NCs that could not be obtained using traditional microbial cultures techniques. Thus, the genetic information of microorganisms is a “gold mine” for “hidden” NCs, which we are now able to exploit using cutting-edge and interdisciplinary methods to discover novel NCs in a high-throughput manner. Identification of silent BGCs followed by their expression by altering the culture conditions and using specific elicitors have been proved a significant technique for the expression of novel NCs in a microtiter plate. Furthermore, LAESI-IMS is cutting edge technique described for the identification of novel NCs directly from the microtiter plate with ultra-accuracy. Various dereplications techniques are also described to enhance the pace of novel NCs discovery. This chapter summarizes the modern techniques for the discovery of novel NCs in a high throughput fashion.