Rational conversion of chromophore selectivity of cyanobacteriochromes to accept mammalian intrinsic biliverdin

Significance Although cyanobacteriochrome photoreceptors are potentially useful molecules for bioimaging and optogenetics because of their compactness and spectral diversity, most cyanobacteriochromes have a drawback to need a chromophore unavailable in the mammalian cells. To overcome this significant drawback, this study focused on a mammalian intrinsic chromophore, biliverdin. We succeeded in conversion of biliverdin-rejective cyanobacteriochromes into biliverdin acceptable molecules by replacement of only four residues. Furthermore, molecular basis for the biliverdin incorporation has been revealed by the X-ray crystallography. One such engineered molecule was shown to function as a near-infrared fluorescent probe for in vivo imaging in living mice. This study provides a rational strategy to obtain molecules applicable to bioimaging and optogenetics.