Considerations of the chemical biology of microbial natural products provide an effective drug discovery strategy

Abstract

Conventional approaches to natural product drug discovery rely mainly on random searches for bioactive compounds using bioassays. These traditional approaches do not incorporate a chemical biology perspective. Searching for bioactive molecules using a chemical and biological rationale constitutes a powerful search paradigm. Here, the authors review recent examples of the discovery of bioactive natural products based on chemical and biological interactions between hosts and symbionts, and propose this method provides a more effective means of exploring natural chemical diversity and eventually of discovering new drugs.

Interpreting Microbial Biosynthesis in the Genomic Age: Biological and Practical Considerations

“…One prevailing hypothesis suggests that genes conveying a fitness benefit (e.g., via the production of an antibiotic natural product) will tend to cluster over evolutionary timeframes due to the importance of their “teamwork” [23] in generating a compound that endows a benefit upon the producing species and/or any of its symbiotic partners. Biosynthetic potential is a function of the environmental chemical landscape [24] and species–species interactions [22,25] that define an organism’s niche. However, the spatial and temporal dynamics of microbial interaction networks and selective forces are largely unknown and rational discovery strategies that leverage ecological interactions have only begun to be employed in a few relatively well-defined systems [4,25,26,27].…”

“…Biosynthetic potential is a function of the environmental chemical landscape [24] and species–species interactions [22,25] that define an organism’s niche. However, the spatial and temporal dynamics of microbial interaction networks and selective forces are largely unknown and rational discovery strategies that leverage ecological interactions have only begun to be employed in a few relatively well-defined systems [4,25,26,27]. …”

Therapeutic applications and biological activities of bacterial bioactive extracts

“…In 1928, Alexander Fleming discovered penicillin from Penicillium chrysogenum previously known as Penicillium notatum which marked the significant shift from plants to microorganisms as a source of natural products (Gaynes 2017 ). Since then, the utilization of microorganism-derived compounds has spread in medicine, agriculture, the food industry and scientific research (Choi and Oh 2015 ). Nowadays, the chemical and biological tools allowed scientists to uncover the biological effects of natural compounds on the human body, as well as to apply possible synergies, which help in developing new therapies (Ji et al 2009 ).…”

Synthesis of Jacaranone-Derived Nitrogenous Cyclohexadienones and Their Antiproliferative and Antiprotozoal Activities

“…About 40% of the chemical scaffolds found in NPs are still absent in today’s medicinal chemistry [ 3 ]. The importance of NPs in drug development has been described in a number of reviews and reports [ 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ].…”