Chemo-enzymatic Production of Specialty Glycans
Lead Research Organisation:
University of Leeds
Department Name: Sch of Chemistry
Abstract
This project will investigate the enzymatic glycosylation of modified carbohydrate monosaccharides to achieve larger, biologically relevant glycan structures. This will be achieved by extensive screening of glycosyltransferase enzymes (enzymes that catalyse the addition of a new monosaccharide to a growing sugar 'acceptor'), that are able to use modified sugars as the 'acceptor', but also as 'donor'.
The biological relevance of the synthesised new type of glycan structures will be validated by investigating their binding profile to a range of proteins that are known to be of relevance in the health sciences, with the immediate aim to develop new diagnostics applications. However, depending on the array results, further applications in other areas in the health sciences are envisaged.
The biological relevance of the synthesised new type of glycan structures will be validated by investigating their binding profile to a range of proteins that are known to be of relevance in the health sciences, with the immediate aim to develop new diagnostics applications. However, depending on the array results, further applications in other areas in the health sciences are envisaged.
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 proposal submitted to IUK
Organisations
- University of Leeds, United Kingdom (Lead Research Organisation)
- EPSRC, United Kingdom (Co-funder)
- University of Southampton, United Kingdom (Collaboration)
- Dextra Laboratories (Collaboration)
- University of Warwick, United Kingdom (Collaboration)
- University of Bristol, United Kingdom (Collaboration)
- Prozomix Ltd. (Collaboration)
- Imperial College London, United Kingdom (Collaboration)
- University of York, United Kingdom (Collaboration)
- Ludger Ltd, United Kingdom (Collaboration)
- Open University, United Kingdom (Collaboration)
- Carbosynth Ltd (Collaboration)
- University of Manchester, Manchester, United Kingdom (Collaboration)
Publications
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
Huang K
(2019)
Enzymatic synthesis of N-acetyllactosamine from lactose enabled by recombinant ß1,4-galactosyltransferases.
in Organic & biomolecular chemistry
Ross JF
(2019)
Directed Assembly of Homopentameric Cholera Toxin B-Subunit Proteins into Higher-Order Structures Using Coiled-Coil Appendages.
in Journal of the American Chemical Society
Valverde P
(2020)
Chemoenzymatic synthesis of 3-deoxy-3-fluoro-l-fucose and its enzymatic incorporation into glycoconjugates.
in Chemical communications (Cambridge, England)
| Description | We have identified novel enzymes that can join together unnatural carbohydrates. We have constructed a library of unnatural analogues of human carbohydrates and used them to develop methods to distinguish between different proteins that bind to the same type of carbohydrate |
| Exploitation Route | For development of novel diagnostic tools for a wide variety of diseases |
| Sectors | Chemicals,Healthcare |
| Title | Dataset associated with "Directed assembly of homo-pentameric globular proteins into high-order structures using coiled-coil appendages" |
| Description | Characterisation data and microscopy images of tubular supra-molecular complexes of cholera toxin B subunit appended with a coiled coil domain. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Description | Chemo-enzymatic Production of Specialty Glycans |
| Organisation | Carbosynth Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | enzymatic synthesis of carbohydrates |
| Collaborator Contribution | synthetic chemistry; microarray construction and analysis |
| Impact | Outputs ongoing. synthetic chemistry; enzymology; molecular biology; microarray analysis |
| Start Year | 2015 |
| Description | Chemo-enzymatic Production of Specialty Glycans |
| Organisation | Dextra Laboratories |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | enzymatic synthesis of carbohydrates |
| Collaborator Contribution | synthetic chemistry; microarray construction and analysis |
| Impact | Outputs ongoing. synthetic chemistry; enzymology; molecular biology; microarray analysis |
| Start Year | 2015 |
| Description | Chemo-enzymatic Production of Specialty Glycans |
| Organisation | Imperial College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | enzymatic synthesis of carbohydrates |
| Collaborator Contribution | synthetic chemistry; microarray construction and analysis |
| Impact | Outputs ongoing. synthetic chemistry; enzymology; molecular biology; microarray analysis |
| Start Year | 2015 |
| Description | Chemo-enzymatic Production of Specialty Glycans |
| Organisation | Ludger Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | enzymatic synthesis of carbohydrates |
| Collaborator Contribution | synthetic chemistry; microarray construction and analysis |
| Impact | Outputs ongoing. synthetic chemistry; enzymology; molecular biology; microarray analysis |
| Start Year | 2015 |
| Description | Chemo-enzymatic Production of Specialty Glycans |
| Organisation | Open University |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | enzymatic synthesis of carbohydrates |
| Collaborator Contribution | synthetic chemistry; microarray construction and analysis |
| Impact | Outputs ongoing. synthetic chemistry; enzymology; molecular biology; microarray analysis |
| Start Year | 2015 |
| Description | Chemo-enzymatic Production of Specialty Glycans |
| Organisation | Prozomix Ltd. |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | enzymatic synthesis of carbohydrates |
| Collaborator Contribution | synthetic chemistry; microarray construction and analysis |
| Impact | Outputs ongoing. synthetic chemistry; enzymology; molecular biology; microarray analysis |
| Start Year | 2015 |
| Description | Chemo-enzymatic Production of Specialty Glycans |
| Organisation | University of Bristol |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | enzymatic synthesis of carbohydrates |
| Collaborator Contribution | synthetic chemistry; microarray construction and analysis |
| Impact | Outputs ongoing. synthetic chemistry; enzymology; molecular biology; microarray analysis |
| Start Year | 2015 |
| Description | Chemo-enzymatic Production of Specialty Glycans |
| Organisation | University of Manchester |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | enzymatic synthesis of carbohydrates |
| Collaborator Contribution | synthetic chemistry; microarray construction and analysis |
| Impact | Outputs ongoing. synthetic chemistry; enzymology; molecular biology; microarray analysis |
| Start Year | 2015 |
| Description | Chemo-enzymatic Production of Specialty Glycans |
| Organisation | University of Southampton |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | enzymatic synthesis of carbohydrates |
| Collaborator Contribution | synthetic chemistry; microarray construction and analysis |
| Impact | Outputs ongoing. synthetic chemistry; enzymology; molecular biology; microarray analysis |
| Start Year | 2015 |
| Description | Chemo-enzymatic Production of Specialty Glycans |
| Organisation | University of Warwick |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | enzymatic synthesis of carbohydrates |
| Collaborator Contribution | synthetic chemistry; microarray construction and analysis |
| Impact | Outputs ongoing. synthetic chemistry; enzymology; molecular biology; microarray analysis |
| Start Year | 2015 |
| Description | Chemo-enzymatic Production of Specialty Glycans |
| Organisation | University of York |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | enzymatic synthesis of carbohydrates |
| Collaborator Contribution | synthetic chemistry; microarray construction and analysis |
| Impact | Outputs ongoing. synthetic chemistry; enzymology; molecular biology; microarray analysis |
| Start Year | 2015 |
| Description | Complex Life of Sugars @ Astbury Conversation |
| 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 | Interactive displays educating the general public about glycoscience |
| Year(s) Of Engagement Activity | 2016,2018 |
| URL | https://twitter.com/wbturnbull/status/986336659708014593 |
| Description | Pint of Science - Complex Life of Sugars |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Presentation and scientific demonstrations for the general public held in a Leeds pub during Leeds Pint of Science Week |
| Year(s) Of Engagement Activity | 2017 |