Synthetic Glycobiology

Bacterial cell-based and cell-free systems for biosynthesis of complex glycans and glycoconjugates

There is an urgent need for new tools to understand the structure, recognition, metabolism, and biosynthesis of glycans as well as the production of biologically important glycans and glycoconjugates. With the discovery of glycoprotein synthesis in bacteria and functional transfer of glycosylation pathways between species, Escherichia coli cells have become a tractable host for both understanding glycosylation and the underlying glycan code of living cells as well as for expressing glycoprotein therapeutics and vaccines. Our group has harnessed natural biological pathways and engineered synthetic designer pathways in bacteria for making complex glycans and conjugating these to lipids and proteins. Our lab’s efforts have resulted in the transformation of bacteria and their cell-free extracts into robust platforms for scalable, bottom-up production of complex glycoconjugates by design.

Notable contributions include: 

(i) creation of eukaryotic protein glycosylation pathways in E. coli cells for N-linked (Nat Chem Biol 2012) and O-linked (Nat Chem Biol 2020) modification, and their optimization using high-throughput flow cytometric screening (Metab Eng 2018)

 

(ii) cell-free glycoprotein synthesis technologies (Nat Commun 2019; Nat Commun 2018; Nat Chem Biol 2018; Glycobiology 2012) with the potential for developing personalized glycomedicines and distributed biomanufacturing

(iii) a suite of powerful genetic screens and selections for studying and engineering glycosylation enzymes (Nat Chem Biol 2018; Nat Chem Biol 2014Biotechnol J 2013; Protein Sci 2010)

Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University

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