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Updated: Jan 16, 2026

A Facile Protocol to Generate Site-Specifically Acetylated Proteins in Escherichia Coli
Published on: December 9, 2017
Advancing Genetically Encoded Lysine (GEK) Chemistry: From Precision Modulation to Therapeutic Innovation
Guoqing Jin1, Yifan Shi1, Shivangi Sharma1
1Texas A&M Drug Discovery Center and Department of Chemistry, College of Arts and Sciences, Texas A&M University, College Station, Texas 77843, United States.
None:
Genetically encoded lysine (GEK) chemistry has transformed protein engineering by enabling precise and site-specific modifications, which expand lysine's functional landscape beyond its native post-translational modifications (PTMs). Our work has systematically advanced GEK chemistry by developing engineered pyrrolysyl-tRNA synthetase (PylRS) variants that efficiently incorporate diverse lysine (Lys) derivatives with tailored chemical reactivity. By integrating bioorthogonal handles, acyl and electrophilic warheads, photo-cross-linking groups, and PTM mimics, we have established a set of powerful toolkits for protein labeling, functional studies, and Lys-directed drug design. These advances provide precise control over protein structure and function, facilitating the study of epigenetic modifications, enzyme-substrate interactions, and Lys-guided inhibitor development. As GEK chemistry continues to evolve, its integration with structural/synthetic biology and therapeutic innovation will further expand its impact, unlocking new frontiers in chemical biology and precision therapeutics.
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