Synthetic Glycobiology: Parts, Systems, and Applications

Weston Kightlinger, Katherine F. Warfel, Matthew P. Delisa, Michael C. Jewett*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Protein glycosylation, the attachment of sugars to amino acid side chains, can endow proteins with a wide variety of properties of great interest to the engineering biology community. However, natural glycosylation systems are limited in the diversity of glycoproteins they can synthesize, the scale at which they can be harnessed for biotechnology, and the homogeneity of glycoprotein structures they can produce. Here we provide an overview of the emerging field of synthetic glycobiology, the application of synthetic biology tools and design principles to better understand and engineer glycosylation. Specifically, we focus on how the biosynthetic and analytical tools of synthetic biology have been used to redesign glycosylation systems to obtain defined glycosylation structures on proteins for diverse applications in medicine, materials, and diagnostics. We review the key biological parts available to synthetic biologists interested in engineering glycoproteins to solve compelling problems in glycoscience, describe recent efforts to construct synthetic glycoprotein synthesis systems, and outline exemplary applications as well as new opportunities in this emerging space.

Original languageEnglish (US)
Pages (from-to)1534-1562
Number of pages29
JournalACS synthetic biology
Volume9
Issue number7
DOIs
StatePublished - Jul 17 2020

Funding

The authors would like to acknowledge Jasmine Hershewe, Ashty Karim, and other members of the Jewett Lab for helpful discussions and feedback. W.K. acknowledges support from the National Science Foundation Graduate Research Fellowship program (DGE-1324585) and the Northwestern University Terminal Year Fellowship. K.F.W. acknowledges support from the National Defense Science and Engineering Graduate (NDSEG) Fellowship program (ND-CEN-013-096). M.C.J. and M.P.D acknowledge support from the Defense Threat Reduction Agency Grant HDTRA1-15-10052/P00001 and HDTRA1-20-10004 and the Bill & Melinda Gates Foundation Grant OPP1217652. M.C.J. also thanks the DARPA 1000 Molecules Program HR0011-15-C-0084, the National Institutes of Health Grant 1U19AI142780-01, the David and Lucile Packard Foundation, and the Camille Dreyfus Teacher-Scholar Program. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of DARPA, Defense Threat Reduction Agency, or the U.S. Government.

Keywords

  • glycoengineering
  • glycosyltransferase
  • protein glycosylation
  • synthetic glycobiology

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Biomedical Engineering

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