JACS: Professor Yang Chaoyong of Xiamen University and Professor Yan Hao of Arizona State University in the United States cooperate to realize the bionic construction of light controlled enzyme pathway

Professor Yang Chaoyong's research group of School of chemistry and chemical engineering of Xiamen University and Professor Yan Hao of Arizona State University in the United States have made progress in the bionic construction of light driven pathway Relevant research results "a synthetic light driven substrata channeling system for precise regulation of enzyme cascade activity based on DNA origin" published by J am Chem SOC （ DOI:10.1021/jacs.8b05429 ）。 The cascade enzyme reactions in vivo have the advantages of fast catalysis, good selectivity and mild reaction conditions, which are of great significance for the fields of synthetic biology and biomedicine As one of the mechanism of the cascade enzyme reaction, the substrate channel directly transfers the metabolic intermediates to the next enzyme through the swing arm to avoid the substrate diffusion into the solution, which not only improves the selectivity of the enzyme reaction, but also greatly accelerates the enzyme reaction rate In order to further understand the mechanism of substrate channel and explore its application in synthetic biology, the research team combined DNA origami and photoresponsive azobenzene molecules to construct a light driven substrate channel system in vitro to regulate the activity of cascade enzyme catalytic reaction DNA origami is a kind of ideal material for the precise assembly and functional regulation of nanoparticles, proteins, small molecules and other objects, because of its precise addressability, nano spatial resolution and excellent dynamic tunability In this work, the square DNA origami structure of 90 nm in length and 60 nm in width was used as the template to realize the precise assembly of G6PDH LDH protease and coenzyme factors, and the horizontal distance between the cascade enzymes could be precisely regulated, so as to regulate the catalytic activity of the cascade enzyme Using the important role of substrate channel in the cascade enzyme reaction, the research team modified photosensitive azobenzene molecules on the swing arm and anchor DNA chain, and controlled the swing direction of NAD + / NADH with the structural light response of azobenzene molecules, so as to achieve fast, reversible and pollution-free regulation of enzyme pathway activity In the visible light, trans azobenzene can promote the hybridization between the swing arm and the anchor point, making coenzyme factor far away from the enzyme pathway, thus reducing the enzyme pathway activity; in the ultraviolet light, trans azobenzene can make the swing arm and the anchor point to hybridize the chain and promote the free swing of coenzyme factor between the cascade enzymes, so as to improve the enzyme pathway activity This strategy realizes the rapid and reversible light regulation of cascade enzyme activity, and provides a new idea of light regulation of protein activity for synthetic biology, biomedicine and other fields This work was completed under the guidance of Professor Yang Zhaoyong, Dr Ke Guoliang (now assistant professor of Hunan University) and Professor Yan Hao The first author is Chen Yahong, a doctoral student of 2016 ichem, and Ma Yanli, a graduate doctoral student, participated in some experiments This work was supported by the National Natural Science Foundation of China and the Ministry of Education (Yangtze River scholars and innovation team development plan).