The majority of the medically important antibiotic drugs are derived from secondary metabolites, which are produced by bacteria and filamentous fungi. Despite intensive world-wide efforts using alternative approaches, no other concept could so far surpass the historically successful strategy to exploit biologically active natural products as candidates for anti-infective drugs. The recently observed, increasing resistance of the human pathogens against antibiotics has prompted us to intensify our search for novel lead structures from microorganisms and fungi, which can be used as anti-infective drugs.
Microbiologists, mycologists, biotechnologists, pharmacists and natural product chemists at the HZI are looking for more effective antibiotics in active ingredient producers that have so far been poorly investigated. They are developing new methods to isolate and culture these diverse species for screening. They also develop genomic information from the producer organisms and use it to exploit the genetic potential of these organisms to form new and modified active substances and to improve their production.
Since 2022, we have been working on a division of labor. While the search for new active ingredients from Myxobacteria and other groups of Eubacteria is ongoing at HIPS (e.g. in the “Microbial Natural Products” department), we at the Braunschweig site are concentrating on discovery of new classes of bioactive natural products from fungi. Improved analytical methods for the search and structure elucidation of secondary metabolites are being developed across the participating groups, even with the Chemical Biology department of the HZI. The extracts obtained from the cultures are examined for new as well as known microbial products using analytical HPLC with UV and MS detection. The new substances are isolated using preparative chromatography and their structure is elucidated using NMR spectroscopy and mass spectrometry. A wide range of tests is used to evaluate the biological effects, selectivity and mechanism of action. Our scientists test the substances they find on pathogenic and multi-resistant bacteria, filamentous fungi, yeasts, cell cultures and enzymes. In addition, the substances are made available to academic and industrial cooperation partners internally and externally for special tests. They can be produced biotechnologically in larger quantities to enable chemical derivatization programs and pharmacological studies in collaboration with other areas within the HZI. To move towards practical application, our scientists cooperate with industrial partners in order to be able to provide the necessary quantities of substances for the first development steps through large-scale fermentation and downstream processing.
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