Optimisation of the lysolipins, potent broad spectrum antibiotics from the actinomycete Streptomyces

15/02/2018 to 14/02/2019

Lysolipin I is an extraordinarily potent antibacterial natural product, with an MIC in the low nanomolar range against Gram-positive organisms and a higher, but still nanomolar MIC against Gram-negative microorganisms. Its mechanism of action is not yet fully understood. However, its usability as antibacterial agent is limited due to the fact that is also shows cytotoxicity. First experiments have shown that structural modifications of the lysolipin core structure can differentially influence antibacterial activity and cytotoxicity.
The aim of the proposed project is to develop a lysolipin derivative as ADMET profiled clinical development candidate by structure optimisation via both chemical and molecular biology strategies in early 2018. This goal will be achieved by a combination of state-of-the-art fermentation technology, natural product analysis and molecular biology with the aim of optimizing the activity as well as the toxicity profile of lysolipin I.