Chemical precision glyco-mutagenesis by glycosyltransferase engineering in living cells
Stacy A. Malaker,
Simon P. Wisnovsky,
Marjoke F. Debets,
Anthony J. Agbay,
Lauren J. S. Wagner,
Douglas M. Fox,
Melissa A. Gray,
Jennifer J. Kohler,
Carolyn R. Bertozzi
Posted 13 Jun 2019
bioRxiv DOI: 10.1101/669861 (published DOI: 10.1016/j.molcel.2020.03.030)
Posted 13 Jun 2019
Studying posttranslational modifications classically relies on experimental strategies that oversimplify the complex biosynthetic machineries of living cells. Protein glycosylation contributes to essential biological processes, but correlating glycan structure, underlying protein and disease-relevant biosynthetic regulation is currently elusive. Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context and glycan fine structure. We introduce a non-natural substrate biosynthetic pathway and use engineered glycosyltransferases to incorporate chemically tagged sugars into the cell surface glycome of the living cell. We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases. This approach bestows a gain-of-function modification on cells where the products of individual glycosyltransferases can be selectively characterized or manipulated at will.
- Downloaded 1,344 times
- Download rankings, all-time:
- Site-wide: 11,704
- In synthetic biology: 135
- Year to date:
- Site-wide: None
- Since beginning of last month:
- Site-wide: 55,287
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!