Goedhart, J. et al. Nat. Commun. 3, 751 (2012).

Cyan fluorescent protein serves as the donor fluorophore for the majority of genetically encoded sensors based on fluorescence resonance energy transfer, and scientists have continuously improved it over the years in an attempt to optimize its performance. Goedhart et al. examined the structures of some of these variants, trying to uncover the origins of these improvements. They noted one highly variable residue that did not appear to be optimized and subjected it to saturation mutagenesis. This resulted in a variant they named monomeric (m)Turquoise2 that exhibits faster maturation and a quantum yield of 93% as well as other beneficial characteristics. The protein's improved characteristics will be useful, but it is becoming clear that optimization of the popular fluorescent protein backbones is entering a period of diminishing returns.