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Going through a phase

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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Fig. 1: Enzymatic processing by the ER and lipid droplet localized hydrolase LDAH controls LasA phase partitioning and cytotoxicity.


  1. Walther, T. C., Chung, J. & Farese, R. V. Jr. Annu. Rev. Cell Dev. Biol. 33, 491–510 (2017).

    Article  CAS  Google Scholar 

  2. Olzmann, J. A. & Carvalho, P. Nat. Rev. Mol. Cell Biol. 20, 137–155 (2019).

    Article  CAS  Google Scholar 

  3. Dubey, R. et al. Nat. Chem. Biol. (2020).

  4. Isbrucker, R. A., Guzmán, E. A., Pitts, T. P. & Wright, A. E. J. Pharmacol. Exp. Ther. 331, 733–739 (2009).

    Article  CAS  Google Scholar 

  5. Horton, P. A., Koehn, F. E., Longley, R. E. & McConnell, O. J. J. Am. Chem. Soc. 116, 6015–6016 (1994).

    Article  CAS  Google Scholar 

  6. Zhang, Y.-W., Ghosh, A. K. & Pommier, Y. Cell Cycle 11, 4424–4435 (2012).

    Article  CAS  Google Scholar 

  7. Goo, Y.-H., Son, S.-H., Kreienberg, P. B. & Paul, A. Arterioscler. Thromb. Vasc. Biol. 34, 386–396 (2014).

    Article  CAS  Google Scholar 

  8. Goo, Y.-H., Son, S.-H. & Paul, A. Sci. Rep. 7, 2743 (2017).

    Article  Google Scholar 

  9. Kory, N. et al. J. Lipid Res. 58, 226–235 (2017).

    Article  CAS  Google Scholar 

  10. Greenwood, D. J. et al. Science 364, 1279–1282 (2019).

    Article  CAS  Google Scholar 

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Correspondence to James A. Olzmann.

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Li, Z., Morris, S.N.S. & Olzmann, J.A. Going through a phase. Nat Chem Biol 16, 111–112 (2020).

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