Borrelidin
B: Isolation, Biological Activity, and
Implications for Nitrile Biosynthesis
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Abstract
Borrelidin (<b>1</b>) is a
nitrile-containing bacterially
derived polyketide that is a potent inhibitor of bacterial and eukaryotic
threonyl-tRNA synthetases. We now report the discovery of borrelidin
B (<b>2</b>), a tetrahydro-borrelidin derivative containing
an aminomethyl group in place of the nitrile functionality in borrelidin.
The discovery of this new metabolite has implications for both the
biosynthesis of the nitrile group and the bioactivity of the borrelidin
compound class. Screening in the SToPS assay for tRNA synthetase inhibition
revealed that the nitrile moiety is essential for activity, while
profiling using our in-house image-based cytological profiling assay
demonstrated that <b>2</b> retains biological activity by causing
a mitotic stall, even in the absence of the nitrile motif