Exploitation of Fungal Biodiversity for Discovery of Novel Antibiotics

Abstract

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.

Regulatory cascade and biological activity of Beauveria bassiana oosporein that limits bacterial growth after host death

“…The discovery of antibiotics in Penicillium crysogenum is well known, and fungi-particularly those occupying unique ecological niches-continue to be a source for their discovery (31,32). Iron-binding siderophores, synthesized via nonribosomal peptide synthase-mediated pathways, are involved in iron scavenging, uptake, and sequestration, and have been shown to act as virulence factors in various pathogenic fungi (33).…”

Actinobacteria and Myxobacteria—Two of the Most Important Bacterial Resources for Novel Antibiotics

“…This heat-shock treatment should dispatch most non-spore forming bacteria to provide the slow growing Actinobacteria a selective benefit for growth. Such measures had to be taken to avoid that, as described in the concurrent paper of Karwehl and Stadler (2016) for fungi, the fast-growing strains in soil samples would inadvertently overgrow the more interesting, hitherto unexploited ones. Afterwards, the samples were diluted in several dilution steps and plated on different types of nutrient rich agar plates.…”

An unprecedented spiro [furan-2,1’-indene]-3-one derivative and other nematicidal and antimicrobial metabolites from Sanghuangporus sp. (Hymenochaetaceae, Basidiomycota) collected in Kenya

“…Fungi have been recognized as source of structurally unique and bioactive metabolites (Karwehl and Stadler, 2016). The fungal diversity in the tropical rainforest ecosystems has been underexplored, since the majority of the fungal species found in these habitats have not been described nor has their chemistry been studied.…”