Virulent organisms possess a variety of biosynthetic pathways creating natural products which contribute to infection. Many virulence factors are produced by type II fatty acid synthase (FAS), polyketide synthase (PKS) or non-ribosomal peptide synthase (NRPS) biosynthetic pathways. Sfp-type phosphopantetheinyl transferases (PPTase) are responsible for activating carrier proteins (CP) in many of these pathways. Associated carrier proteins require post-translational transfer of a phosphopantetheine from Coenzyme A (CoA) to operate correctly. We utilize fluorescent analogs of CoA in high-throughput screening (HTS) format capable of detecting inhibition of Sfp activity, in addition to related virulent PPTases. By inhibiting pathogenic PPTase activity and curtailing natural product synthesis, we hope to develop new drugs against these organisms.

Fluorescent-based inhibitor screening for Sfp-type PPTases

243rd National Meeting (2012)

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