Protein-based biosensors have long been used for biodetection by transforming biological events into readily measurable electronic or optical signals (Castillo et al., 2004). A large number of fusion protein-based biosensors are built from fluorescent proteins, such as GFP and its spectral variants. By tracking changes in the fluorescent properties of a single FP or fluorescence resonance energy transfer (FRET) efficiency between two FPs, these biosensors have been extensively used in vivo or in vitro, including live-cell imaging of cellular events, protein phosphorylation, calcium ion signaling and heavy metal ion detection ( Snapp, 2001). Fluorescent protein-based biosensors may contain a single fluorescent protein or FRET donor/acceptor pairs, coupled with a polypeptide chain that undergoes conformational changes upon binding of a target of interest (Frommer et al., 2009). One example of single GFP-based biosensor has been presented by Amaro et al. (2014) who fused GFP with a metallothionein from Tetrahymena thermophila to detect cadmium ions. When exposed to Cd2 +, the cells overexpressed this fusion protein, resulting in marked resistance to cadmium toxicity.