Research Programs of Glycoscience in the Wang Lab Synthetic Biology: Glycomedicine: Chemical Biology of Carbohydrates: 1. Green chemistry and approach to produce pharmaceuticals and chemicals 2. Biosynthetic engineering to produce sugar-protein conjugates 1.Natural and synthetic glycolipids and glycoconjugates as medicines 2.Glycoproteins as vaccines and medicines 1.Basic research on carbohydrate processing enzymes and glycomics 2.Basic research on biosynthesis and biogenesis of complex carbohydrates 1. Natural and Synthetic Glycolipids and Glycoconjugates as Medicines 1. Glycosyltransferases and glycomics 1. Green chemistry and approach to produce pharmaceuticals and chemicals Our Lab has a longstanding expertise in chemical and/or enzymatic synthesis of natural glycolipids and natural product glycoconjugates which have remarkable biological significance. The following are selected representatives of products which have been accomplished in recent years. General glycosyltransferase (GT) catalyzed reaction: GT transfers sugar from nucleotide diphoshate (NDP) sugar to an acceptor Donor substrate DHAP is expensive and unstable. Phosphate group should be removed to obtain the desired product. Flask to E.coli Applications of glycosyltransferases: Glycomics: comprehensive study of structures and functions of carbohydrates Elucidate biosynthetic pathways Biosynthesis of complex carbohydrates 2. Biosynthesis and Biogenesis of Lipopolysaccharide (LPS) phosphatase OH OH HO HO O E.Coli Machinery O HO HO aldolase OH OH Core AcHN HO O AcHN O OH OH O O HO O OH HO O O O HO O HO HO HO O HO OH O OH HO O HO OH O OH OH OH OH O OH OH HO O OH HO O O O P O HO O O O O HO OH O O O O P O O O AcNH n O O OH O OH AcNH OH HO HO OH HO O COO OH HO O O O COO O-antigen acch polys aride O O P O O OO Lipid A O O O O O HN HO O O O O O HO O 2. Glycoproteins as vaccines and medicines O HN O O P O O HO 2. Biosynthetic engineering to produce sugar-protein conjugates The structure of Lipopolysacchride (LPS) Wzy-dependent O-antigen synthesis in E. coli Wzy expression Lipid Undecaprenol Expression and activity assay of membrane protein Wzy and Wzz Geometry 7 cis, 3 trans Structure Percent (%) 3 O 51 ± 5 7 Heptaprenol 4 cis, 2 trans 34 ± 4 Pentaprenol 2 cis, 2 trans 15 ± 2 Cis-Pentaprenol 4 cis, 0 trans 29 ± 4 Solanesol 0 cis, 8 trans 0 MS-Pentaprenol 1 cis, 2 trans 3±1 Comparison of Wzy activity among repeating unit donors with variable lipid moieties. Bacterial cell surface polysaccharides, such as lipopolysaccharides (LPSs) play important roles in processes critical to bacterial pathogenicity and immunology. The Wang group has set up a platform to biosynthesize bacterial lipopolysaccharide using purified key proteins Wzy and Wzz in vitro. Through this approach, the biochemical property of those important enzymes will be studied (P.G Wang, et al. Nat. Chem. Biol. 2010, 6, 418–423). E. coli O157-CRM197 glyco-conjugate vaccine S. penumoniae 23F-CRM197 glyco-conjugate vaccine 1. Funding Support: • Research and Development of a Novel System to Produce Polysaccharide Vaccines (NIH R01) • Biosynthesis of Polysaccharides (NIH R01 GM085267) • Investigation on Oligosaccharides as Antimicrobial and Prebiotics (NIH R01 HD061935) 2. Wang Lab Members: • PI: Dr. Peng George Wang • Research Scientists: Dr. Lirong Chen, Dr. Jing Song, Dr. Baolin Wu; Postdocs: Dr. Tiehai Li, Dr. Guilong Zhao, Dr. Guohui Zhao; Graduate students: Jarin Joyner, Xu Li, Xifang Liu, Elena Nikonova, Xuan Wang, Mohui Wei, Adriel Williams, Zhongying Xiao, Baoyuan Zhang, Qing Zhang 3. Contact Information • Website: http://chemistry.gsu.edu/P_Wang.php • Contact information: P. G. Wang (pwang11@gsu.edu)