Silent pathway awakening to discover novel antibacterial compounds from actinomycetes
At a glance
- Project leader : Prof. Dr. Martin Sievers
- Co-project leader : Dr. Joël Pothier
- Deputy of project leader : Prof. Dr. Rainer Riedl
- Project team : Fabienne Arn, David Frasson, Dr. Ivana Kroslakova, Dr. Fabio Rezzonico, Steven Schmitt, Dennis Wipfli, Dr. Irene Wüthrich
- Project budget : CHF 250'000
- Project status : completed
- Funding partner : Internal
- Contact person : Martin Sievers
Description
There is a tremendous need for novel antibiotics due to the global resistance crisis. Actinomycetes are the most important sources of secondary metabolites. They provide an enormous potential to discover novel antibiotics. Actinobacteria remain an underexploited reservoir of interesting products, especially regarding new compounds because genomic studies have revealed that they have a greater potential to produce natural products than previously expected. Novel approaches are applied to activate the production of new antibacterial compounds from selected actinomycetes strains which are developed into new drugs. Most biosynthetic gene clusters responsible for producing secondary metabolites remain silent in the absence of particular stimuli and are not expressed under standard cultivation conditions. These silent biosynthetic gene clusters represent a promising source for the discovery of novel antimicrobial compounds. A challenge that will be addressed collectively in this project is to activate the production of novel secondary metabolites and further develop the detected compounds into new antibiotic drugs. Genome mining strategies and the use of small molecule chemical elicitors will be used to unlock the production of novel compounds. The SpheroBiotics technology allows the cultivation of selected strains in the laboratory under their natural environment to enable the fast identification of promissing molecules.
Further information
Publications
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Pothier, Joël F.; Bolt, Valentin; Arn, Fabienne; Frasson, David; Rhyner, Nicola; Sievers, Martin,
2023.
Microbiology Resource Announcements.
12(3), pp. e01225-22.
Available from: https://doi.org/10.1128/mra.01225-22