This review adds
the bilin-binding phytochromes to the Chemical Reviews thematic issue “Optogenetics and
Photopharmacology”. The work is structured into two parts.
We first outline the photochemistry of the covalently bound tetrapyrrole
chromophore and summarize relevant spectroscopic, kinetic, biochemical,
and physiological properties of the different families of phytochromes.
Based on this knowledge, we then describe the engineering of phytochromes
to further improve these chromoproteins as photoswitches and review
their employment in an ever-growing number of different optogenetic
applications. Most applications rely on the light-controlled complex
formation between the plant photoreceptor PhyB and phytochrome-interacting
factors (PIFs) or C-terminal light-regulated domains with enzymatic
functions present in many bacterial and algal phytochromes. Phytochrome-based
optogenetic tools are currently implemented in bacteria, yeast, plants,
and animals to achieve light control of a wide range of biological
activities. These cover the regulation of gene expression, protein
transport into cell organelles, and the recruitment of phytochrome-
or PIF-tagged proteins to membranes and other cellular compartments.
This compilation illustrates the intrinsic advantages of phytochromes
compared to other photoreceptor classes, e.g., their bidirectional
dual-wavelength control enabling instant ON and OFF regulation. In
particular, the long wavelength range of absorption and fluorescence
within the “transparent window” makes phytochromes attractive
for complex applications requiring deep tissue penetration or dual-wavelength
control in combination with blue and UV light-sensing photoreceptors.
In addition to the wide variability of applications employing natural
and engineered phytochromes, we also discuss recent progress in the
development of bilin-based fluorescent proteins.