The Impending Renaissance in Discovery & Development of Natural Products

Abstract

Antibiotics are wonder drugs. Unfortunately, owing to overuse, antibiotic resistance is now a serious problem. Society now finds itself in the post-antibiotic era, and the threat of infectious diseases is on the rise. New antibiotics are sorely needed. There is strong evidence that suggests natural products are an attractive source of new antimicrobials. They posses desirable structural and chemical properties that make them potent thearpeutics. However, steep tehnological challenges associated with screening and manufacturing these molecules has stifled the discovery, development and marketing of new antimicrobials. To this end, two recent scientific developments are poised to redress this situation. The recent development of metagenomics and ancillary high-throughput screening technologies has exponentiated the volume of useful genetic sequence information that can be screened for antimicrobial discovery. These approaches have been instrumental in the discovery of new antibiotics from soil and marine environments. Secondly, a new manufacturing paradigm employing metabolic engineering as its engine has greatly accelerated the path to market for these molecules, in addition to improving the atom and energy economy of antimicrobial manufacturing. We outine these developments in this review, and provide a perspective on integrating next-generation approaches such as metagenomics and metabolic engineering with traditional methodologies for discovering and manufacturing antimicrobial natural products in order to unleash a rennaissance in the discovery and development of antimicrobials.

Culture-Dependent Bioprospecting of Bacterial Isolates From the Canadian High Arctic Displaying Antibacterial Activity

“…Antimicrobial resistance has steadily increased in clinical settings (Bitnun and Yeh, 2018). We are on the cusp of returning to a pre-antibiotic world in which common infections and minor injuries will once again become deadly (Laxminarayan et al, 2013; Ferri et al, 2017; Pawar et al, 2017). Simultaneously, natural product discovery efforts on the part of the pharmaceutical industry have largely dwindled since the end of the 20th century (Baker et al, 2007).…”

Identification by Genome Mining of a Type I Polyketide Gene Cluster from Streptomyces argillaceus Involved in the Biosynthesis of Pyridine and Piperidine Alkaloids Argimycins P

“…The recent development of genomics, metagenomics and high-throughput screening has increased exponentially the volume of useful genetic sequence information that can be employed for natural products discovery. Additionally, a new manufacturing paradigm employing metabolic engineering and synthetic biology as its engine has greatly accelerated the path of development for microbial natural product drugs ( Rutledge and Challis, 2015 ; Katz and Baltz, 2016 ; Pawar et al, 2016 ). Genome mining consists of searching a genome for genes that encode enzymes involved in a particular process.…”

Natural Cyclopeptides as Anticancer Agents in the Last 20 Years

“…From ancient times, taking Chinese Medicine as an example, people have been familiar with medicinal properties of natural resources and the benefits of using them to treat diseases [8]. Hence, due to their extraordinary chemical diversity with different origins, natural products are of great potential to be developed as new drugs for cancer prevention and treatment [9].…”