Xanthopsin-Like Systems via Site-Specific Click-Functionalization of a Retinoic Acid Binding Protein

The use of light-responsive proteins to control both living or synthetic cells, is at the core of the expanding fields of optogenetics and synthetic biology. It is thus apparent that a richer reaction toolbox for the preparation of such systems is of fundamental importance. Here, we provide a proof-of-principle demonstration that Morita-Baylis-Hillman adducts can be employed to perform a facile site-specific, irreversible and diastereoselective click-functionalization of a lysine residue buried into a lipophilic binding pocket and yielding an unnatural chromophore with an extended pi-system. In doing so we effectively open the path to the in vitro preparation of a library of synthetic proteins structurally reminiscent of xanthopsin eubacterial photoreceptors. We argue that such a library, made of variable unnatural chromophores inserted in an easy-to-mutate and crystallize retinoic acid transporter, significantly expand the scope of the recently introduced rhodopsin mimics as both optogenetic and lab-on-a-molecule tools.

Automated summary

The use of Morita-Baylis-Hillman adducts allows for facile site-specific, irreversible, and diastereoselective click-functionalization of a lysine residue, producing an unnatural chromophore with an extended pi-system within a lipophilic binding pocket. This approach opens up the possibility of in vitro preparation of a library of synthetic proteins structurally reminiscent of xanthopsin eubacterial photoreceptors, expanding the scope of optogenetic and lab-on-a-molecule tools introduced by rhodopsin mimics.