Chemo-enzymatic Production of Specialty Glycans
Lead Research Organisation:
University of Leeds
Department Name: Sch of 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 proposal submitted to IUK
Organisations
- University of Leeds (Lead Research Organisation)
- EPSRC (Co-funder)
- OPEN UNIVERSITY (Collaboration)
- UNIVERSITY OF YORK (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
- University of Warwick (Collaboration)
- Carbosynth Ltd (Collaboration)
- UNIVERSITY OF MANCHESTER (Collaboration)
- Prozomix Ltd. (Collaboration)
- Dextra Laboratories (Collaboration)
- Ludger Ltd (Collaboration)
- University of Southampton (Collaboration)
- University of Bristol (Collaboration)
People |
ORCID iD |
| Bruce Turnbull (Principal Investigator) |
Publications
Hollingsworth K
(2023)
A 'glyco-fluorine' code revealing differential recognition by glycan binding partners
Hollingsworth K
(2024)
Synthesis and screening of a library of Lewisx deoxyfluoro-analogues reveals differential recognition by glycan-binding partners.
in Nature communications
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 | Glycofluoroform microarray |
| Description | a microarray of fluorinated glycans at Imperial College London that can distinguish between proteins that recognise the same parent glycan. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2024 |
| Provided To Others? | Yes |
| Impact | ability to distinguish between bacterial toxins that recognise the same parent glycan. |
| Title | CCDC 1922810: Experimental Crystal Structure Determination |
| Description | Related Article: Pablo Valverde, Jean-Baptiste Vendeville, Kristian Hollingsworth, Ashley P. Mattey, Tessa Keenan, Harriet Chidwick, Helene Ledru, Kler Huonnic, Kun Huang, Mark E. Light, Nicholas Turner, Jesús Jiménez-Barbero, M. Carmen Galan, Martin A. Fascione, Sabine Flitsch, W. Bruce Turnbull, Bruno Linclau|2020|Chem.Commun.|56|6408|doi:10.1039/D0CC02209H |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | Data supports the published paper |
| URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc22jv4m&sid=DataCite |
| 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 |
| Title | Glycofluoroforms of Lewis-x |
| Description | Analytical data of the synthesis of a set of lewis-x glycofluoroforms. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2024 |
| Provided To Others? | Yes |
| Impact | data supports the published paper |
| URL | https://archive.researchdata.leeds.ac.uk/1316/ |
| 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 | "Re-engineering the Biology of Sugars", Café Scientifique |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Public understanding of science talk |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.cafe-sci.org.uk/previous-events/?event_id1=140 |
| 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 |