Chemo-enzymatic Production of Specialty Glycans
Lead Research Organisation:
University of Manchester
Department Name: Chemistry
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
The vision of the project centres around the translation of traditional and novel methodologies to develop sustainable and versatile platforms for the industrial production of glycans on scale. We will demonstrate the technology by targeting a set of novel glycan materials that are anticipated to have significant transformational potential in human health and disease in diagnostics and glycoengineering applications. This project requires an integrated approach featuring: 1) synthetic chemistry (unnatural building blocks) 2) biocatalysis (enzymatic synthesis of larger glycans) 3) showcasing glycan potential in diagnostics (glycoarray based platforms). The significant anticipated progression of both biocatalysis and glycoarray technologies will reduce commercialisation barriers both in terms of commercial glycan production and 'first in the market' glycan array companies.
Planned Impact
As described in the submission of the PI
People |
ORCID iD |
| Sabine Flitsch (Principal Investigator) |
Publications
Bulmer G
(2021)
A promiscuous glycosyltransferase generates poly-ß-1,4-glucan derivatives that facilitate mass spectrometry-based detection of cellulolytic enzymes
in Organic & Biomolecular Chemistry
Cioce A
(2022)
Cell-specific bioorthogonal tagging of glycoproteins
in Nature Communications
Cosgrove S
(2019)
Biocatalytic Oxidation in Continuous Flow for the Generation of Carbohydrate Dialdehydes
in ACS Catalysis
Ford GJ
(2020)
Synthesis of protected 3-aminopiperidine and 3-aminoazepane derivatives using enzyme cascades.
in Chemical communications (Cambridge, England)
France S
(2016)
Constructing Biocatalytic Cascades: In Vitro and in Vivo Approaches to de Novo Multi-Enzyme Pathways
in ACS Catalysis
Gonzalez-Rodriguez E
(2023)
O-Linked Sialoglycans Modulate the Proteolysis of SARS-CoV-2 Spike and Likely Contribute to the Mutational Trajectory in Variants of Concern.
in ACS central science
Gray CJ
(2019)
Advancing Solutions to the Carbohydrate Sequencing Challenge.
in Journal of the American Chemical Society
Gray CJ
(2020)
Mass spectrometry hybridized with gas-phase InfraRed spectroscopy for glycan sequencing.
in Current opinion in structural biology
Huang K
(2019)
Enzymatic synthesis of N-acetyllactosamine from lactose enabled by recombinant ß1,4-galactosyltransferases.
in Organic & biomolecular chemistry
Huang K
(2018)
Characterisation of a Bacterial Galactokinase with High Activity and Broad Substrate Tolerance for Chemoenzymatic Synthesis of 6-Aminogalactose-1-Phosphate and Analogues.
in Chembiochem : a European journal of chemical biology
Huang K
(2020)
Biochemical characterisation of an a1,4 galactosyltransferase from Neisseria weaveri for the synthesis of a1,4-linked galactosides.
in Organic & biomolecular chemistry
Keenan T
(2020)
Profiling Substrate Promiscuity of Wild-Type Sugar Kinases for Multi-fluorinated Monosaccharides.
in Cell chemical biology
Keenan T
(2019)
The characterisation of a galactokinase from Streptomyces coelicolor.
in Carbohydrate research
Lv Y
(2017)
Highly efficient and selective biocatalytic production of glucosamine from chitin
in Green Chemistry
Mattey A
(2019)
Selective Oxidation of N -Glycolylneuraminic Acid Using an Engineered Galactose Oxidase Variant
in ACS Catalysis
Mattey AP
(2020)
Natural heterogeneous catalysis with immobilised oxidase biocatalysts.
in RSC advances
Pallister E
(2020)
Enzyme promiscuity of carbohydrate active enzymes and their applications in biocatalysis.
in Current opinion in structural biology
Thomas B
(2017)
Application of Biocatalysis to on-DNA Carbohydrate Library Synthesis
in ChemBioChem
Valverde P
(2020)
Chemoenzymatic synthesis of 3-deoxy-3-fluoro-l-fucose and its enzymatic incorporation into glycoconjugates.
in Chemical communications (Cambridge, England)
Weise N
(2020)
Bi-enzymatic Conversion of Cinnamic Acids to 2-Arylethylamines
in ChemCatChem
Yan C
(2017)
Real-Time Screening of Biocatalysts in Live Bacterial Colonies.
in Journal of the American Chemical Society
| Description | New synthetic routes to fluorinated sugars using chemo-enzymatic strategies. Awaiting results on binding assays. |
| Exploitation Route | Results of this project can be used in follow up work to probe carbohydrate-carbohydrate and carbohydrate-protein interactions. |
| Sectors | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Description | BBSRC The Great British Biosciences Festival, 14-16th November 2014 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Professor Sabine Flitsch was successful in her bid to host "The Complex Life of Sugars" at BBSRC The Great British Biosciences Festival, 14-16th November 2014, London. The exhibition was visited by over 6,500 visitors including people from the following categories: students, teachers, public, scientists, media, potential donors/key decision makers and celebrities. One of the main exhibition activities was focused on cell surface sugars and visitors were encouraged to build a cell surface sugar and explore its interaction with cell invaders both on a cell surface and also a gold glycan array. For more contents please visit our blog http://sugar-complexity.tumblr.com/ and twitter feed @sugarcomplexity. |
| Year(s) Of Engagement Activity | 2014 |
| Description | Gateways Widening Participation Event |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | The activities included glycan building through arts-and-crafts, enzymatic glucose testing and a luminol demonstration, with all activities linked to the science of blood - something familiar to all the students attending. This helped high-school students to link classroom science to the real world and explore different options as a career in science. It also integrated current research topics form this project and the wider research institute. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Manchester Institute of Biotechnology Open Day, 8th November 2013 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | The MIB Open Day was specifically aimed at A-Level students nationally. The day focused on hands-on experiments and lectures to promote working at the interface between chemistry and biology to solve problems with a biological 'green' solution and encourage science students to pick applied science subjects. The feedback was very positive with pupils reporting that they now realized there were a lot more options for further study and jobs than they previously knew about. |
| Year(s) Of Engagement Activity | 2013 |
| Description | New Scientist Live (EXCEL London) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | 22,476 visitors, 81 pieces of news coverage, 208 journalists attended and reached 623 million people - we had visitors following up asking for resources which we have made into an activity pack for schools. |
| Year(s) Of Engagement Activity | 2016 |
| URL | https://live.newscientist.com/ |
| Description | Royal Society Satellite Science Exhibition (Manchester Museum of Science and Industry) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Family friendly hands on exhibition "The Complex Life of Sugars" showcasing stands from previous Royal Society Summer Science Exhibitions, estimated attendance at the stand, over 200 people per day for 5 days |
| Year(s) Of Engagement Activity | 2016 |
| URL | https://royalsociety.org/science-events-and-lectures/science-exhibition-manchester/ |
| Description | Science Spectacular, Manchester Museum 2nd November 2014 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | The Science Spectacular is aimed at families to promote sciences as fun and useful. The feedback from individuals questioned were all positive, reporting changes in their opinions and behaviour and more pupils expressing an interest in studying science further. |
| Year(s) Of Engagement Activity | 2014 |
| Description | ScienceX (The Trafford Centre Manchester) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | ScienceX was part of Manchester City of Science/ESOF. We took hands on experiments including sugar building and smelling compounds in cola which can be made using biotechnology. It reached passers-by at The Trafford Centre and an audience that would not normally attend science exhibitions. The participants said that they did not like science at school and then really enjoyed the activities and discussions. It gave lots of people more confidence in their scientific abilities. |
| Year(s) Of Engagement Activity | 2016 |
| Description | The Science Spectacular, Manchester Museum, 2nd November 2013 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | The Royal Society Summer Science Exhibition proved so popular that we were asked to be part of The Science Spectacular, 2nd November 2013 at The Manchester Museum http://www.manchestersciencefestival.com/whatson/science-spectacular. The Science Spectacular was aimed primarily at young children and families to encourage children to enjoy science. The feedback from parents was very positive. |
| Year(s) Of Engagement Activity | 2013 |
| URL | http://www.manchestersciencefestival.com/whatson/science-spectacular |