## 3 Results and Discussion
### BLUF Proteins for Optogenetic Tools  
Small photoreceptors, such as sensors of blue light using flavin (BLUF), light oxygen voltage (LOV) based receptors and cryptochromes, have been identified in the genomes of different organisms, from prokaryotes to higher eukaryotes, as has been shown in the present study and in several other studies [160; 161]. As evident from the present study and other in vitro experiments [161; 162; 163; 164; 165], one of the peculiar features of these light-sensitive motifs are their association with various effector domains, thus hinting about the wide range of novel mechanistic and functional diversity controlled by light. This aspect is yet to be studied in detail. Investigations into PixJ1 (blue and green light), RcaE (red and green), changes in light-dependent _E. gracilis_ PAC-\(\alpha\) activity for _Drosophila_, behavioral modulation and neural responses in marine gastropod _Aplysia_ and _Caenorhabditis elegans_[166; 167; 168; 169; 170; 171] suggest sensitivities of each receptor toward a particular light bandwidth, which can be one of the important tools used to engineer a novel system for a broad range of physiological outputs. This study further expands the possibilities for the BLUF domain to be used as a powerful optogenetic tool for the development of novel optogenetic technologies. A vast variety of domain combinations of BLUF photoreceptors in different genomes (Figure 1) represents a promising and valuable tool to design novel photo-regulated enzymes, messengers, photo-modulation of gene expression patterns, photo-control of the virulence in pathogenic bacteria through the recombinant expression of such systems, photobehavioural responses in photobacteria, modulation of neural systems and dynamic molecular switches to regulate biological activities. BLUF domains, in combination with the EAL, GGDEF or CHD domains, could be utilized for the photo-dependent regulation of c-di-GMP and cAMP associated signaling in bacteria [64; 85]. The BLUF domain associated with a B\({}_{12}\) binding domain has also been analyzed; however, it does not show the important amino acids that are required in order to form the binding pocket for AdoB\({}_{12}\). [PERSON] et al. [92] also reported a similar BLUF module and suggested that the associated B\({}_{12}\) binding domain also has a photosensory function which can regulate activity in response to light. The B\({}_{12}\) binding domain broadens the absorption range for the BLUF photosensor, which could be critical to several regulatory pathways [96; 172]. We could also use this modular combination for the photo-dependent regulation of pathways like carotenoid synthesis or photosystem biosynthesis [92]. Another combination which could be engineered and used for an optogenetic application is the association of the BLUF domain with the DNA pol III \(\gamma\) III domain. Using this modular architecture, we could regulate the actions of different components involved in DNA replication in a light-dependent manner. Furthermore, the BLUF domain is also found in association with the p450 (cytochrome p450) domain, which could be used as an optogenetic tool for the light-dependent regulation of several pathways like fatty acid metabolism and secondary metabolism. The optogenetic potential of the BLUF domain could also be acquired in the two-component regulatory system for both prokaryotes and eukaryotes. A modular architecture in which the BLUF sensor domain is associated with the Rec (receiver) domain could be exploited as a two-component regulatory system for the photo-dependent regulation of processes like bacterial chemotaxis and other regulatory pathways [118]. The optogenetic potential of the BLUF domain could also be extended to the regulation of the efflux pump and transporter involved in antibiotic resistance, tolerance to a toxic chemical, synthesis of an osmoprotectant, quorum sensing, drug resistance and sporulation [120; 121; 122].