Genetic screens uncover a bioactivation pathway for Lasonolide A involving enrichment in lipid droplets and cleavage into a cytotoxic, soluble metabolite by a lipid droplet-associated serine hydrolase. These findings identify enzymatically regulated phase partitioning as a drug activation mechanism.
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References
Walther, T. C., Chung, J. & Farese, R. V. Jr. Annu. Rev. Cell Dev. Biol. 33, 491–510 (2017).
Olzmann, J. A. & Carvalho, P. Nat. Rev. Mol. Cell Biol. 20, 137–155 (2019).
Dubey, R. et al. Nat. Chem. Biol. https://doi.org/10.1038/s41589-019-0447-7 (2020).
Isbrucker, R. A., Guzmán, E. A., Pitts, T. P. & Wright, A. E. J. Pharmacol. Exp. Ther. 331, 733–739 (2009).
Horton, P. A., Koehn, F. E., Longley, R. E. & McConnell, O. J. J. Am. Chem. Soc. 116, 6015–6016 (1994).
Zhang, Y.-W., Ghosh, A. K. & Pommier, Y. Cell Cycle 11, 4424–4435 (2012).
Goo, Y.-H., Son, S.-H., Kreienberg, P. B. & Paul, A. Arterioscler. Thromb. Vasc. Biol. 34, 386–396 (2014).
Goo, Y.-H., Son, S.-H. & Paul, A. Sci. Rep. 7, 2743 (2017).
Kory, N. et al. J. Lipid Res. 58, 226–235 (2017).
Greenwood, D. J. et al. Science 364, 1279–1282 (2019).
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Li, Z., Morris, S.N.S. & Olzmann, J.A. Going through a phase. Nat Chem Biol 16, 111–112 (2020). https://doi.org/10.1038/s41589-019-0448-6
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DOI: https://doi.org/10.1038/s41589-019-0448-6