Example：10.1021/acsami.1c06204 or Chem. Rev., 2007, 107, 2411-2502
Genetically Encoded Benzoyllysines Serve as Versatile Probes for Interrogating Histone Benzoylation and Interactions in Living Cells ACS Chemical Biology (IF5.1), Pub Date : 2021-10-07, DOI: 10.1021/acschembio.1c00614 Hongtao Tian, Jiale Yang, An-Di Guo, Yu Ran, Yun-Zhi Yang, Bing Yang, Ruimin Huang, Haiming Liu, Xiao-Hua Chen
Histone posttranslational modifications (PTMs) are vital epigenetic regulators in many fundamental cell signaling pathways and diverse biological processes. Histone lysine benzoylation is a recently identified epigenetic mark associated with active transcription; however, it remains to be explored. Herein, we first report the genetic encoding of benzoyllysine and fluorinated benzoyllysines into full-length histone proteins in a site-specific manner in live cells, based on our rationally designed synthetase and fine-integrated fluorine element into benzoyllysines. The incorporated unnatural amino acids integrating unique features were demonstrated as versatile probes for investigating histone benzoylation under biological environments, conferring multiplex signals such as 19F NMR spectra with chemical clarity and fluorescence signals for benzoylation. Moreover, the site specifically incorporated lysine benzoylation within native full-length histone proteins revealed distinct dynamics of debenzoylation in the presence of debenzoylase sirtuin 2 (SIRT2). Our developed strategy for genetic encoding of benzoyllysines offers a general and novel approach to gain insights into interactions of site-specific histone benzoylation modifications with interactomes and molecular mechanisms in physiological settings, which could not be accessible with fragment histone peptides. This versatile chemical tool enables a direct and new avenue to explore benzoylation, interactions, and histone epigenetics, which will provide broad utilities in chemical biology, protein science, and basic biology research.