The historical delivery of antibiotics from microbial natural products—Can history repeat?

Microbial natural products are the origin of most of the antibiotics on the market today. However, research in antibiotics and natural products has declined significantly during the last decade as a consequence of diverse factors, among which the lack of interest of industry in the field and the strong competition from collections of synthetic compounds as source of drug leads. As a consequence, there is an alarming scarcity of new antibiotic classes in the pipelines of the pharmaceutical industry. Still, microbial natural products remain the most promising source of novel antibiotics, although new approaches are required to improve the efficiency of the discovery process. The impact of microbial biodiversity, the influence of growth conditions on the production of secondary metabolites, the choice of the best approach at the screening step and the challenges faced during the isolation and identification of the active compounds are examined in this review as the critical factors contributing to success in the effort of antibiotic discovery from microbial natural products.