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Front. Chem. | doi: 10.3389/fchem.2020.00645

Cell-free synthetic glycobiology: designing and engineering glycomolecules outside of living cells Provisionally accepted The final, formatted version of the article will be published soon. Notify me

 Matthew P. DeLisa1*,  Thapakorn Jaroentomeechai1,  May N. Taw1, Mingji Li1,  Alicia Aquino1, Ninad Agashe1 and Sean Chung1
  • 1Cornell University, United States

Glycans and glycosylated biomolecules are directly involved in almost every biological process as well as the etiology of most major diseases. Hence, glycoscience knowledge is essential to efforts aimed at addressing fundamental challenges in understanding and improving human health, protecting the environment and enhancing energy security, and developing renewable and sustainable resources that can serve as the source of next-generation materials. While much progress has been made, there remains an urgent need for new tools that can overexpress structurally uniform glycans and glycoconjugates in the quantities needed for characterization and that can be used to mechanistically dissect the enzymatic reactions and multi-enzyme assembly lines that promote their construction. To address this technology gap, cell-free synthetic glycobiology has emerged as a simplified and highly modular framework to investigate, prototype, and engineer pathways for glycan biosynthesis and biomolecule glycosylation outside the confines of living cells. From nucleotide sugars to complex glycoproteins, we summarize here recent efforts that harness the power of cell-free approaches to design, build, test, and utilize glyco-enzyme reaction networks that produce desired glycomolecules in a predictable and controllable manner. We also highlight novel cell-free methods for shedding light on poorly understood aspects of diverse glycosylation processes and engineering these processes towards desired outcomes. Taken together, cell-free synthetic glycobiology represents a promising set of tools and techniques for accelerating basic glycoscience research (e.g., deciphering the ‘glycan code’) and its application (e.g., biomanufacturing high-value glycomolecules on demand).

Keywords: Glycosylation, Glycoengineering, Metabolic Engineering, Synthetic Biology, Cell-free protein synthesis (CFPS), Chemical glycobiology, Glycan, Chemoenzymatic synthesis

Received: 06 Mar 2020; Accepted: 22 Jun 2020.

Copyright: © 2020 DeLisa, Jaroentomeechai, Taw, Li, Aquino, Agashe and Chung. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Matthew P. DeLisa, Cornell University, Ithaca, United States,