Antituberculosis thiophenes define a requirement for Pks13 in mycolic acid biosynthesis

@inproceedings{Wilson2013AntituberculosisTD,
  title={Antituberculosis thiophenes define a requirement for Pks13 in mycolic acid biosynthesis},
  author={Regina Rachael Wilson and Pradeep Kumar and Vijay Parashar and Catherine Vilch{\'e}ze and Romain Veyron-Churlet and Joel S. Freundlich and Samantha Barnes and John R. Walker and Michael J. Szymonifka and Emily J Marchiano and Shubhada Shenai and Roberto Colangeli and William R. Jacobs and Matthew B Neiditch and Laurent Kremer and David Alland},
  booktitle={Nature chemical biology},
  year={2013}
}
We report a new class of thiophene (TP) compounds that kill Mycobacterium tuberculosis by the previously uncharacterized mechanism of Pks13 inhibition. An F79S mutation near the catalytic Ser55 site in Pks13 conferred TP resistance in M. tuberculosis. Overexpression of wild-type Pks13 resulted in TP resistance, and overexpression of the Pks13(F79S) mutant conferred high resistance. In vitro, TP inhibited fatty acyl-AMP loading onto Pks13. TP inhibited mycolic acid biosynthesis in wild-type M… CONTINUE READING
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Citations

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The Molecular Genetics of Mycolic Acid Biosynthesis.

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