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Self-resistance guided genome mining uncovers new topoisomerase inhibitors from myxobacteria.
Panter, Fabian Krug, Daniel Baumann, Sascha Müller, Rolf
Panter, Fabian
Krug, Daniel
Baumann, Sascha
Müller, Rolf
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2018-06-07
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Abstract
There is astounding discrepancy between the genome-inscribed production capacity and the set of known secondary metabolite classes from many microorganisms as detected under laboratory cultivation conditions. Genome-mining techniques are meant to fill this gap, but in order to favor discovery of structurally novel as well as bioactive compounds it is crucial to amend genomics-based strategies with selective filtering principles. In this study, we followed a self-resistance guided approach aiming at the discovery of inhibitors of topoisomerase, known as valid target in both cancer and antibiotic therapy. A common host self-defense mechanism against such inhibitors in bacteria is mediated by so-called pentapeptide repeat proteins (PRP). Genes encoding the biosynthetic machinery for production of an alleged topoisomerase inhibitor were found on the basis of their collocation adjacent to a predicted PRP in the genome of the myxobacterium
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2041-6520
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Attribution-NonCommercial-ShareAlike 3.0 United States