Recently, Tan Minjia, a research group of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and the Ye Bangce Research Group of East China University of Science and Technology, have jointly discovered a new mechanism for the regulation of protein lysine acylation in the biosynthetic metabolic pathway of natural products. The research work was published in August. Cell Chemical Biology (25(8): 984-995. doi: 10.1016/j.chembiol.2018.05.005) and May ACS Chemical Biology (13(5):1200-1208. doi: 10.1021/acschembio.7b01068) on. An important intermediate metabolite acyl-CoA compound, which acts as a donor directly involved in protein acylation modification in vivo, thereby regulating a variety of important biological processes, such as epigenetics, energy metabolism, sperm development, etc., is currently a life science research. One of the hot spots. In the biosynthesis of secondary metabolites in organisms, the role of acyl-CoA has been recognized as a synthetic precursor of many important natural products such as polyketones, alkaloids, fatty acids and isoprene. At present, people's cognition of the role of acylation modification donors in the regulation of secondary metabolite synthesis is obviously insufficient. Two articles, respectively, are propionyl-CoA-dependent macrolides, erythromycin, malonyl-CoA-dependent polyphenols, and polybutyryl-CoA-dependent butanol biosynthesis. The acylation modification, malonylation modification and butyrylation modification were the research objects. The formation mechanism and regulation function of protein acylation modification in the biosynthesis process of natural products with different chemical skeleton types were systematically analyzed by proteomics techniques. It is proved that the accumulation of high concentration of acyl-CoA in the organism can help to supplement the synthesis precursor of the product, and also cause feedback regulation caused by protein acylation modification, leading to inhibition of key enzymes and affecting product yield. This state of imbalance of metabolism due to the "overload" of intracellular metabolite concentration is widely present in the biosynthesis process of natural products of many different chemical skeleton types, and exists in the synthesis pathway of endogenous products and synthetic pathways of artificially constructed products. in. In addition, further studies have shown that post-translational modification metabolic engineering strategies (PTM_ME) based on acylation of modified substrates and modified enzymes, such as protection of modification sites, optimization of modified enzyme systems, etc., help to alleviate intracellular carbon flux "overload" The pressure to relatively increase the target product yield. These two studies have for the first time revealed the universality of protein acylation modification in the regulation of secondary metabolite biosynthesis, and provided a new strategy for metabolic engineering transformation from post-translational modification level. Tan Minjia and Ye Bangce are co-authors of the two articles. Xu Junyu, a postdoctoral fellow at the Shanghai Institute of Materia Medica, and Xu Ya, a doctoral student at East China University of Science and Technology, collaborated under the guidance of two teachers to complete the project. Also participating in this work are the Ye Yang Research Group of the Shanghai Pharmaceutical Institute and Zhao Yingming, a professor at the University of Chicago. In addition, the project is supported by the National Natural Science Foundation's major research projects, face projects, national key research and development programs, "precise medical research" key projects and China's postdoctoral science fund. Source: Shanghai Institute of Materia Medica Potassium Salt,Potassium Oxalate,Oxalic Acid Anhydrous,Oxalic Acid Monohydrate Wuxi Yangshan Biochemical Co.,Ltd. , https://www.salesacetates.com
Progress in protein acylation modification to regulate biosynthesis of natural products
:2018-08-23