The specific and covalent labeling of fusion proteins with synthetic mols. opens up new ways to study protein function in the living cell. Here the authors present a novel method that allows for the specific and exclusive extracellular labeling of proteins on the surfaces of live cells with a large variety of synthetic mols. including fluorophores, protein ligands, or quantum dots. The approach is based on the specific labeling of fusion proteins of acyl carrier protein with synthetic mols. through post-translational modification catalyzed by phosphopantetheinetransferase. The specificity and versatility of the labeling should allow it to become an important tool for studying and manipulating cell surface proteins and for complementing existing approaches in cell surface engineering. [on SciFinder (R)]