Solving Blue Light Riddles: New Lessons from Flavin‐binding LOV Photoreceptors

Detection of blue light (BL) via flavin‐binding photoreceptors (Fl‐Blues) has evolved throughout all three domains of life. Although the main BL players, that is light, oxygen and voltage (LOV), blue light sensing using flavins (BLUF) and Cry (cryptochrome) proteins, have been characterized in great detail with respect to structure and function, still several unresolved issues at different levels of complexity remain and novel unexpected findings were reported. Here, we review the most prevailing riddles of LOV‐based photoreceptors, for example: the relevance of water and/or small metabolites for the dynamics of the photocycle; molecular details of light‐to‐signal transduction events; the interplay of BL sensing by LOV domains with other environmental stimuli, such as BL plus oxygen‐mediating photodamage and its impact on microbial lifestyles; the importance of the cell or chromophore redox state in determining the fate of BL‐driven reactions; the evolutionary pathways of LOV‐based BL sensing and associated functions through the diverse phyla. We will discuss major novelties emerged during the last few years on these intriguing aspects of LOV proteins by presenting paradigmatic examples from prokaryotic photosensors that exhibit the largest complexity and richness in associated functions.