Development of New Synthetic and Analytical Tools in Glycobiotechnology
In the Flitsch lab. we have developed, and are continuing to expand, a toolbox for the synthesis and analysis of complex carbohydrates in order to understand their function. The main focusses of this research are:
(i) glycoarrays to study glycoenzyme activity and discover carbohydrate-protein interactions
(ii) ion mobility mass spectrometry for high resolution structural analysis of carbohydrates
(iii) mass spectrometry for the label free identification of carbohydrate-binding proteins
(iv) chemoenzymatic synthesis of glycoconjugates (glycopeptides, glycolipids, etc.)
Gray C. J; Thomas B, Upton R, Migas L. G, Eyers C. E, Barran P. E and Flitsch S. L. “Applications of ion mobility mass spectrometry for high throughput, high resolution glycan analysis.” BIOCHIMICA AT BIOPHYSICA ACTA (BBA) – GENERAL SUBJECTS. DOI: 10.1016/J.BBAGEN.2016.02.003 – FEB 6 2016.
Both, P.; Green, A. P.; Gray, C. J.; Sardzik, R.; Voglmeir, J.; Fontana, C.; Austeri, M.; Rejzek, M.; Richardson, D.; Field, R. A.; Widmalm, G.; Flitsch, S. L.; Eyers, C. E. Discrimination of epimeric glycans and glycopeptides using IM-MS and its potential for carbohydrate sequencing. NATURE CHEMISTRY. 6(1); 65 – 74. DOI 10.1038/NCHEM.1817 – JAN 2014
Sardzik, Robert; Green, Anthony P.; Laurent, Nicolas; Both, Peter; Fontana, Carolina; Voglmeir, Josef; Weissenborn, Martin J.; Haddoub, Rose; Grassi, Paola; Haslam, Stuart M.; Widmalm, Goran; Flitsch, Sabine L. Chemoenzymatic Synthesis of O-Mannosylpeptides in Solution and on Solid Phase. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. 134(10); 4521 – 4524. DOI 10.1021/ja211861m – MAR 14 2012
Castangia, Roberto; Austeri, Martina; Flitsch, Sabine L. Enzymatic Amine Acyl Exchange in Peptides on Gold Surfaces. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. 51(52); 13016 – 13018. DOI 10.1002/anie.201205404 – 2012
Enzymatic Cascades in Biocatalysis
Through the use of modern molecular biology techniques, it is possible to transfer individual enzymes from their host organism and produce them in more amenable laboratory strain bacteria. This allows them to be more easily studied, engineered and integrated into new enzyme cascades, both in whole cell systems and as cell-free formulations. In the Flitsch group we are interested in the tailoring of various enzymes to perform specific, synthetically-useful reactions and incorporating these into bespoke pathways for the production of industrially- and biomedically-relevant compounds. Examples of target products of particular interest include high value chiral amines as pharmaceutical / fine chemical precursors and glycoconjugates as chemical biology probes for glycobiotechnology.
P. Both, H. Busch, P. P. Kelly, F. G. Mutti, N. J. Turner, S. L. Flitsch, Sabine. Whole-Cell Biocatalysts for Stereoselective C-H Amination Reactions. J. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION., 55; 1511 – 1513.DOI: 10.1002/anie.201510028– JAN 22 2016
Noble, Gavin T.; Craven, Faye L.; Voglmeir, Josef; Sardzik, Robert; Flitsch, Sabine L.; Webb, Simon J. Accelerated Enzymatic Galactosylation of N-Acetylglucosaminolipids in Lipid Microdomains. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. 134(31); 13010 – 13017. DOI 10.1021/ja302506t – AUG 8 2012
Rannes, Julie B.; Ioannou, Avgousta; Willies, Simon C.; Grogan, Gideon; Behrens, Carsten; Flitsch, Sabine L.; Turner, Nicholas J. Glycoprotein Labeling Using Engineered Variants of Galactose Oxidase Obtained by Directed Evolution. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. 133(22); 8436 – 8439. DOI 10.1021/ja2018477 – JUN 8 2011