Development and Applications of D‐Amino Acid Derivatives‐based Metabolic Labeling of Bacterial Peptidoglycan

Abstract Peptidoglycan, an essential component within the cell walls of virtually all bacteria, is composed of glycan strands linked by stem peptides that contain D‐amino acids. The peptidoglycan biosynthesis machinery exhibits high tolerance to various D‐amino acid derivatives. D‐amino acid derivatives with different functionalities can thus be specifically incorporated into and label the peptidoglycan of bacteria, but not the host mammalian cells. This metabolic labeling strategy is highly selective, highly biocompatible, and broadly applicable, which has been utilized in various fields. This review introduces the metabolic labeling strategies of peptidoglycan by using D‐amino acid derivatives, including one‐step and two‐step strategies. In addition, we emphasize the various applications of D‐amino acid derivative‐based metabolic labeling, including bacterial peptidoglycan visualization (existence, biosynthesis, and dynamics, etc.), bacterial visualization (including bacterial imaging and visualization of growth and division, metabolic activity, antibiotic susceptibility, etc.), pathogenic bacteria‐targeted diagnostics and treatment (positron emission tomography (PET) imaging, photodynamic therapy, photothermal therapy, gas therapy, immunotherapy, etc.), and live bacteria‐based therapy. Finally, a summary of this metabolic labeling and an outlook is provided.