For protein localization studies, enzymes can be fused to proteins in the same way as fluorescent protein tags such as GFP. Tissues can be fixed and exposed to chemical substrates that covalently modify the enzyme tags with fluorescent molecules. This approach avoids problems often associated with detecting fluorescent protein tags with antibodies while providing a fast detection method.

The figure shows the use of four commercially available enzyme-substrate systems: SNAP, CLIP, TMP and Halo.

Methods are described in Kohl et al. 2014. Ultrafast tissue staining with chemical tags. PNAS 111: E3805-E3814 and Sutcliffe et al. 2017. Second-Generation Drosophila Chemical Tags: Sensitivity, Versatility, and Speed. Genetics 205:1399-1408.

The following table shows stocks for expressing enzyme-tagged proteins that can be detected with these chemical substrates.