Chemo-enzymatic Production of Specialty Glycans
Lead Research Organisation:
University of Southampton
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
People |
ORCID iD |
| Bruno Linclau (Principal Investigator) | |
| Seung Lee (Co-Investigator) |
Publications
Council C
(2020)
Enzymatic glycosylation involving fluorinated carbohydrates
in Organic & Biomolecular Chemistry
Fontenelle CQ
(2018)
Isolation and characterisation of an unexpected byproduct in the regioselective butane diacetal protection of a-methyl galactopyranoside.
in Carbohydrate research
Hollingsworth K
(2023)
A 'glyco-fluorine' code revealing differential recognition by glycan binding partners
Keenan T
(2020)
Profiling Substrate Promiscuity of Wild-Type Sugar Kinases for Multi-fluorinated Monosaccharides.
in Cell chemical biology
Keenan T
(2023)
Reverse thiophosphorylase activity of a glycoside phosphorylase in the synthesis of an unnatural Manß1,4GlcNAc library
in Chemical Science
Malassis J
(2019)
Synthesis of vicinal dideoxy-difluorinated galactoses.
in Organic & biomolecular chemistry
Poškaite G
(2023)
Obtaining Pure 1 H NMR Spectra of Individual Pyranose and Furanose Anomers of Reducing Deoxyfluorinated Sugars
in The Journal of Organic Chemistry
Richards SJ
(2020)
Introducing affinity and selectivity into galectin-targeting nanoparticles with fluorinated glycan ligands.
in Chemical science
Song HW
(2019)
Surface display of sialyltransferase on the outer membrane of Escherichia coli and ClearColi.
in Enzyme and microbial technology
| Description | We have been able to incorporate fluorinated carbohydrates into glycans through enzymatic glycosylation procedures. We have shown, using a small library of fluorinated analogues of a particular glycan, that the binding profile shows great variation, and is different between related proteins. Then, we have been able to synthesise a much larger library (150 members) of fluorinated analogues of a trisaccharide glycan (Lewis x), with upscaling of 24 member subset. Array screening studies involving a diverse set of proteins, which all interact with Lewis x, clearly showed that multiple fluorination within the glycan leads to distinct fingerprint binding profiles. |
| Exploitation Route | Others will make use of our findings to synthesise custom glycans with a wide variety of fluorination patterss |
| Sectors | Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Description | We have obtained a small Impact acceleration grant to explore commercialisation of a number of fluorinated sugar derivatives. |
| First Year Of Impact | 2021 |
| Sector | Chemicals,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Economic |
| Description | BL keynote at Oxford |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Invited Keynote Speaker at 22st International Symposium on Fluorine Chemistry, Oxford (UK) ("Investigations on the lipophilicity of fluorinated aliphatic compounds") |
| Year(s) Of Engagement Activity | 2018 |
| Description | BL talk Galway |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Invited talk at University of Galway, Ireland ("Synthesis, properties, and biological activities of polyfluorinated carbohydrates") |
| Year(s) Of Engagement Activity | 2018 |
| Description | Direct selective b-glycosylation of fluorinated levoglucosan derivatives (poster EUROCARB) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | poster presentation of Jean-Baptiste Vendeville at EUROCARB, Barcelona, 2-6/07/2017 |
| Year(s) Of Engagement Activity | 2017 |
| Description | ESBOC-glycobiology, Gregynog |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invityed speaker at the annual ESBOC-glycobiology meeting, this time in Gregynog, "Exploring physical properties of carbohydrate derivatives: lipophilicities of fluorinated monosaccharides" |
| Year(s) Of Engagement Activity | 2019 |
| Description | GlycoBasque meeting March 19 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited speaker at the annual GlycoBasque meeting, CIC bioGUNE, Bilbao (Spain), "How fluorination modifies carbohydrate hydrogen bonding properties and lipophilicity" |
| Year(s) Of Engagement Activity | 2019 |
| Description | How to Commercialise your research and turn your glycoscience into a glyco-biotech strat up |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | Workshop organised by IBCarb |
| Year(s) Of Engagement Activity | 2016 |
| Description | JB poster Oxford |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Poster presentation: "Synthesis of dideoxy-fluorinated carbohydrates", The 22nd International Symposium of Fluorine Chemistry, 22nd to 27th of July 2018, oxford |
| Year(s) Of Engagement Activity | 2018 |
| Description | Presentation at CARBO XXXIV |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Invited presentation at the International Carbohydrate Conference CARBO - XXXIV, Lucknow (India), "Insights in carbohydrate lipophilicity" |
| Year(s) Of Engagement Activity | 2019 |
| Description | Presentation at EUROCARB |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Speaker at EUROCARB XX, Leiden (NL), "Lipophilicities of fluorinated carbohydrates and derivatives" |
| Year(s) Of Engagement Activity | 2019 |
| Description | Synthesis and properties of fluorinated carbohydrates (CARBO Delhi) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Plenary Speaker at International Conference on New Frontiers in carbohydrate Chemistry and Biology, Delhi (India), 14-16/11/2016 |
| Year(s) Of Engagement Activity | 2016 |
| Description | Synthesis of stereochemically defined fluorohydrins and polyfluorinated carbohydrates, and investigations on the impact of fluorination on hydrogen bond/lipophilicity and protein binding properties (Leeds Uni) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Invited seminar in Leeds, 10/05/2016 |
| Year(s) Of Engagement Activity | 2016 |
| Description | The Influence of Aliphatic Fluorination on Lipophilicity and Hydrogen Bond Properties of Alcohols and carbohydrates (Maynooth) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Invited Seminar at Maynooth University (06/06/2017) |
| Year(s) Of Engagement Activity | 2017 |
| Description | The Influence of Aliphatic Fluorination on Lipophilicity and Hydrogen Bond Properties of Alcohols: Application in Carbohydrates (Basel) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Invited Seminar at the Basler Chemische Gesellshaft |
| Year(s) Of Engagement Activity | 2017 |