Basic research on carbohydrate processing enzymes and glycomics

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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)
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