Several optogenetic tools have been developed in recent years, yet few systems are available that employ red light for photoactivation. Phytochrome B (PhyB)-Phytochrome interacting factor (PIF) is a unique system, in which PhyB binds to PIF under red light illumination, while PhyB-PIF complex dissociates upon infra-red light illumination. However, PhyB-PIF system requires phycocyanobilin, which is a chromophore of light harvesting in photosynthetic organisms, and therefore purification and addition of PCB are needed to render cells sensitive to red/infra-red light in this system. To overcome this issue, we attempt to reconstitute PCB biosynthesis in mammalian cells for developing a fully genetically-encoded optogenetic system with red/infra-red light. Further, by using this system, we try to manipulate intracellular signalings in space and time by red/infra-red light illumination.