In situ modification of FR900359 biosynthesis in Chromobacterium vaccinii MWU205 René Richarz, Gabriele M. König and Max Crüsemann University of Bonn, Germany FR900359 (FR) (Figure 1) is an eight-membered, cyclic depsipeptide, which belongs to a small and specialized group of natural products named chromodepsins. So far, FR production has been reported from two different bacteria, the obligate plant symbiont “ Candidatus Burkholderia crenata” and the free-living Chromobacterium vaccinii MWU205. In both cases a non-ribosomal peptide synthetase (NRPS) machinery is responsible for its assembly. 1,2 FR has proven to be an excellent tool for the investigation of Gq protein-coupled signaling pathways, that regulate important cellular processes in diverse organisms. 3 This activity also makes it a potential drug lead for the treatment of diseases, such as asthma or cancer. 1 Due to these interesting features there is a strong desire for new FR derivatives with altered activities. This includes the targeting of signaling pathways regulated by other G protein family members as well as the installation of chemical groups for the selective modification of the FR scaffold. Here we report our first results on the in situ modification of FR biosynthesis by C.vaccinii to generate altered FR molecules.
Figure 1: Structure of FR900359. References 1. C. Hermes, G. M. König and M. Crüsemann, Nat. Prod. Rep. , 2021, 38 , 2276-2292.
2. C. Hermes, R. Richarz, D. A. Wirtz, J. Patt, W. Hanke, S. Kehraus, J. H. Voss, J. Küppers, T. Ohbayashi, V. Namasivayam, J. Alenfelder, A. Asuka Inoue, P. Mergaert, M. Gütschow, E. Kostenis, G. M. König and M. Crüsemann, Nat. Commun., 2021, 12 , 144. 3. R. Schrage, A.-L. Schmitz, E. Gaffal, S. Annala, S. Kehraus, D. K. Wenzel, G. M. König and E. Kostenis, Nat. Commun., 2015, 6 , 10156.
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