Rodriguez, S. & Wolfgang, M.J. Chem. Biol. 19, 391–398 (2012).

There is increased interest in the development of methods that allow direct regulation of protein activity in vivo and monitoring of the process. Rodriguez & Wolfgang achieve this by using a chemical-genetic approach. The team targeted the metabolic enzyme malonyl-CoA decarboxylase by fusing its gene to that encoding FK506 binding protein 12, rendering the protein fusion stable only in the presence of the small molecule Shield-1. They tagged the protein fusion with YFP to monitor stabilization of the protein. In addition, the researchers engineered the entire transgene so that it could be conditionally regulated by Cre recombinase and included two additional fluorescent proteins: CFP as a marker of transgene expression, and monomeric (m)Cherry as a marker of recombination. They used the approach to alter fatty acid metabolism in live mice.