Lipoic Acid Ligase A‐Mediated Ligation: Mechanism, Applications, and Emerging Innovations in Bioconjugation

Abstract

This review outlines the latest findings on bioconjugation using lipoic acid ligase A (LplA), a key enzyme that allows the introduction of new functional groups into biomolecules. LplA functions via a characteristic mechanism of covalently binding orthologous lipoic acid derivatives in vivo to a specific 13 amino acid sequence called the LplA acceptor peptide (LAP). This unique functionality has enabled a wide range of applications, including cell‐surface modification, protein immobilization, fluorescent labeling of antibodies. Recently, the modification of proteins without LAP sequences has been demonstrated, suggesting their potential for future biopharmaceutical production. Although several review articles on enzyme ligation have been published, research on LplA remains limited. This review attempts to fill this gap by introducing LplA based on its mechanism, applications, and recent research reports.

Biological Evaluation of Antibody-Drug Conjugates Produced by Tag-Free Lipoate Ligase A Modification

“…In the past few years, momentum has shifted toward tag-free enzymatic protein modification, a direction our research group has eagerly embraced. Our interest lies primarily in lipoate ligase A (LplA), − which has been acknowledged for its ability to modify the primary amine of lysine via an amidation procedure using short chain fatty acids. Historically, the LplA function has been found to depend on an LAP tag to guide it to the target Lys .…”