Abstract: Provided herein are compositions and systems comprising complementation-based tags and reporters for labeling and detection of targets by luminescence and a second modality (e.g., fluorescence), and methods of use thereof. In particular, tags are provided comprising the fusion of a first component of bioluminescent complex and a first component of modified dehalogenase complex, reporters are provided comprising the second component of bioluminescent complex and the second component of modified dehalogenase complex, and systems and methods are provided comprising the tags and reporters herein for dual-modality labeling and detection of targets.

Abstract: Provided herein are peptide and polypeptide sequences that structurally assemble to form active, modified dehalogenase structures capable of binding to a haloalkyl ligand. In particular, provided herein are split dehalogenase variants that assemble through structural complementation into active dehalogenase complexes, and systems and methods of use thereof.

Abstract: Provided herein modified dehalogenases have extended surface loop regions that provide a location for internal fusion insertions and modulate binding interaction and activation of environmentally-sensitive chemistries.