Lanthanide-Controlled Protein Switches: Development and In Vitro and In Vivo Applications

Lanthanides, which are part of the rare earth elements group have numerous applications in electronics, medicine and energy storage. However, our ability to extract them is not meeting the rapidly increasing demand. The discovery of the bacterial periplasmic lanthanide-binding protein lanmodulin spurred significant interest in developing biotechnological routes for lanthanide detection and extraction. Here we report the construction of β-lactamase-lanmodulin chimeras that function as lanthanide-controlled enzymatic switches. Optimized switches demonstrated dynamic ranges approaching 3000-fold and could accurately quantify lanthanide ions in simple colorimetric or electrochemical assays. E.coli cells expressing such chimeras grow on β-lactam antibiotics only in the presence of lanthanide ions. The developed lanthanide-controlled protein switches represent a novel platform for engineering metal-binding proteins for biosensing and microbial engineering.