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CSSB Seminar Series - Rolf Müller

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https://desy.zoom.us/j/99356506620
Meeting ID: 993 5650 6620
Passcode: 348386

Abstract

Amongst the well-established bacterial producers, myxobacteria have a great track record for the discovery of entirely new natural product scaffolds exhibiting promising bioactivities. (1) This is at least in part because they have been much less studied as compared to other traditional sources such as actinomycetes and bacilli. Comparisons of myxobacterial metabolite profiles with the number of underlying biosynthetic gene clusters encoded in their very large genomes show, that many compounds still remain unknown. (2) Further, recent studies indicate that the order of myxobacteria likely comprises many more biodiverse representatives than previously assumed. According to metagenomics analyses, myxobacteria (including many underexplored representatives) are highly abundant in the soil microbiome, where they play a crucial role in soil nutrient and carbon cycling. Taken together with our recent genomic analyses, these findings suggest that the biosynthetic potential of myxobacteria is a long way from being exhausted.

Nevertheless, the issue of rediscovery is a major hurdle for myxobacterial extracts as well. In an attempt to tackle this issue, we recently demonstrated that chemical diversity correlates with taxonomic distance in myxobacteria. (3) Accordingly, we are more likely to isolate novel compound classes from strains which are phylogenetically distant from previously characterized strains as compared to closely related strains. This knowledge can be applied to prioritize strains for natural product discovery, thus increasing the chance of discovering compound classes with yet unknown chemical structures and biological activities. I will discuss recent results from our laboratory regarding the identification, structure elucidation, biosynthesis and mode of action of bioactive natural products from (myxo)bacteria based on different approaches, and will show our recent advances in their preclinical development. (4,5,6,7,8)

 

  1. 1. Herrmann et al. 2017, Nat. Prod. Rep. 34 (2), 135–160
  2. 2. Hug et al. 2020, Nat. Rev. Chem. 4, 172-193
  3. 3. Hoffmann et al. 2018, Nat. Commun. 9 (1), 803
  4. 4. Baumann et al. 2014, Angew. Chem. Int. Ed. 53 (52), 14605–14609
  5. 5. Hüttel et al. 2017, Angew. Chem. Int. Ed. Engl. 56 (41), 12760–12764
  6. 6. Pogorevc et al. 2019, Metab. Eng. 55, 201–211
  7. 7. Groß et al. 2021, Nat. Commun. 12, 1696
  8. 8. Panter et al. 2021, Angew. Chem. Int. Ed., in press