AbstractはじめにNAD は生体内補酵素として広く用いられている．それ以外に，NAD は寿命延伸に関わる Sirtuin や，国立研究開発法人理化学研究所 環境資源科学研究センターケミカルバイオロジー・生合成研究チーム・チームディレクターRIKEN Center for Sustainable Resource Science,Chemical Biology and Biosynthesis Research Team淡川 孝義Takayoshi Awakawa― 177 ―NAD is widely used as a coenzyme in living organisms. In addition, NAD serves as a substrate for important proteins involved in physiological functions such as Sirtuin, which is associated with lifespan extension, and poly ADP-ribose polymerase PARP, which is involved in genome repair, or as a substrate for RNA cap structure modification reactions, among other functions. It is known to perform diverse physiological functions (Molecules 24, 4187, 2019; Nat. Commun. 6, Article number 8332, 2015). The authors reported for the first time that NAD serves as a substrate in the biosynthesis of the antitumor azindane natural product altemicidin, thereby demonstrating its novel role 1). In this biosynthetic pathway, the nicotinamide moiety of NAD undergoes a nucleophilic attack by PLP enzymes (SbzP/PseP), followed by the formation of two C-C bonds between the C3 and C2 units, resulting in modification (Figure 1). This nicotinamide moiety undergoes further modification, with the hydrolysis of a phosphate bond leading to the formation of an NMN-like structure that activates Sirtuin function, followed by additional multi-step modifications to yield the final product. In this study, we performed precise functional analysis of SbzP enzyme and its product-modifying enzymes using cryo-electron microscopy and X-ray crystal structure analysis. By modifying their functions, we expanded the structural diversity of the products and obtained new active compounds using enzymatic and chemical methods.新規補酵素代謝経路の利用による医薬品活性分子の創出Creation of active pharmaceutical molecules through the utilization of new coenzyme metabolic pathways
元のページ ../index.html#179