Chemo-enzymatic Production of Specialty Glycans
Lead Research Organisation:
University of York
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 proposal submitted to IUK
People |
ORCID iD |
Martin Fascione (Principal Investigator) |
Publications
Chidwick HS
(2021)
Reconstitution and optimisation of the biosynthesis of bacterial sugar pseudaminic acid (Pse5Ac7Ac) enables preparative enzymatic synthesis of CMP-Pse5Ac7Ac.
in Scientific reports
Chidwick HS
(2020)
Mechanistic and structural studies into the biosynthesis of the bacterial sugar pseudaminic acid (Pse5Ac7Ac).
in Organic & biomolecular chemistry
Cioce A
(2022)
Cell-specific bioorthogonal tagging of glycoproteins
in Nature Communications
Keenan T
(2020)
Profiling Substrate Promiscuity of Wild-Type Sugar Kinases for Multi-fluorinated Monosaccharides.
in Cell chemical biology
Keenan T
(2021)
A Tale of Two Bioconjugations: pH Controlled Divergent Reactivity of Protein a-oxo-Aldehydes in Competing a-oxo-Mannich and Catalyst-Free Aldol Ligations.
in ACS chemical biology
Keenan T
(2019)
The characterisation of a galactokinase from Streptomyces coelicolor.
in Carbohydrate research
Keenan T
(2023)
Reverse thiophosphorylase activity of a glycoside phosphorylase in the synthesis of an unnatural Manß1,4GlcNAc library.
in Chemical science
Richards S
(2021)
Introducing affinity and selectivity into galectin-targeting nanoparticles with fluorinated glycan ligands
in Chemical Science
Description | The key finding of this award is that enzymes can be used to build unnatural complex carbohydrates containing fluorine atoms. These 'glycofluoroforms' can then be used to fingerprint binding profiles of different proteins with the same carbohydrate. The tools developed in this award including new substrates and products and novel reactivity modes of known enzymes could have applications in the future in development of new biosensor and diagnostics. |
Exploitation Route | The outcomes of this award may have relevance in the future in development of new biosensor and diagnostics, and the production of enzymes for the scalable production of complex unnatural carbohydrates. |
Sectors | Chemicals Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
Description | BBSRC IBCarb NIBB Proof of Concept funds |
Amount | £100,000 (GBP) |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 02/2016 |
End | 11/2016 |
Description | Research Collaboration |
Organisation | University of Manchester |
Department | Manchester Institute of Biotechnology MIB |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Supply of kinase enzymes for modification of sugars |
Collaborator Contribution | Supply of enzymes and carbohydrate substrates |
Impact | Publication in preparation |
Start Year | 2017 |