Phenolic Substitution in Fidaxomicin: A Semisynthetic Approach to Antibiotic Activity Across Species

Jung, Erik; Kraimps, Anastassia; Dittmann, Silvia; Griesser, Tizian; Costafrolaz, Jordan; Mattenberger, Yves; Jurt, Simon; Viollier, Patrick H; Sander, Peter; Sievers, Susanne; Gademann, Karl

doi:10.1002/cbic.202300570

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Jung, E., Kraimps, A., Dittmann, S., Griesser, T., Costafrolaz, J., Mattenberger, Y., Jurt, S., Viollier, P. H., Sander, P., Sievers, S., & Gademann, K. (2023). Phenolic Substitution in Fidaxomicin: A Semisynthetic Approach to Antibiotic Activity Across Species. Chembiochem, 24(24), e202300570. https://doi.org/10.1002/cbic.202300570

Abstract

Fidaxomicin (Fdx) is a natural product antibiotic with potent activity against Clostridioides difficile and other Gram-positive bacteria such as Mycobacterium tuberculosis. Only a few Fdx derivatives have been synthesized and examined for their biological activity in the 50 years since its discovery. Fdx has a well-studied mechanism of action, namely inhibition of the bacterial RNA polymerase. Yet, the targeted organisms harbor different target protein sequences, which poses a challenge for the rational development of new semisyntheti