How to Overcome the Antibiotic Crisis

Sabrina Karwehl, Marc Stadler, Karwehl, Sabrina, Stadler, Marc

Fungi were among the first sources for antibiotics. The discovery and development of the penicillin-type and cephalosporin-type β-lactams and their synthetic versions were transformative in emergence of the modern pharmaceutical industry. They remain some of the most important antibiotics, even 70 years after their discovery. Meanwhile, thousands of fungal metabolites have been discovered, yet these metabolites have only contributed a few additional compounds that have entered clinical development. Substantial expansion in fungal biodiversity assessment along with the availability of modern "-OMICS" technology and revolutionary developments in fungal biotechnology have been made in the last 15 years subsequent to the exit of most of the big Pharma companies from the field of novel antibiotics discovery. Therefore, the timing seems opportune to revisit these fascinating chemically rich organisms as a reservoir of small-molecule templates for lead discovery. This review will describe ongoing interdisciplinary scenarios in which specialists in fungal biology collaborate with chemists, pharmacologists and biochemical and process engineers in order to reveal and make new antibiotics. The utility of a pre-selection process based on phylogenetic data and distribution of secondary metabolite encoding gene cluster will be highlighted. Examples of novel bioactive metabolites from fungi derived from special ecological groups and new phylogenetic lineages will also be discussed.