Glycoenzymes for Bioindustries
Lead Research Organisation:
Quadram Institute
Department Name: Gut Microbes and Health
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 project will translate existing academic work on the development of novel glycoenzymes to produce a suite of stable/robust enzymes at scale to address the current gaps in certain commercially available specificities. The lack of availability of such enzymes is a major barrier to those wishing to utilise them for diagnostics, synthesis or chemical modification processes often necessitating de novo synthesis of the enzyme targeting the required reaction before development/evaluation of the process can begin. Each academic partner will develop a subset of the glycoenzyme classes, providing the necessary analytical expertise to characterise and optimise the enzymes. Underpinning this work will be genome mining combined with enzyme evolution to discover/develop novel microbial sourced enzymes displaying desired activities. Industry input to the project will guide the development of the enzymes whilst ensuring that they are fit for purpose and brought to market to allow end user access.
Planned Impact
As described in proposal submitted to IUK
People |
ORCID iD |
Nathalie Juge (Principal Investigator) |
Publications
Wu H
(2021)
Fucosidases from the human gut symbiont Ruminococcus gnavus.
in Cellular and molecular life sciences : CMLS
Wu H
(2023)
Structure and function of microbial a-l-fucosidases: a mini review.
in Essays in biochemistry
Gascueña A
(2023)
Exploring the sequence-function space of microbial fucosidases
Duan CJ
(2020)
Ascertaining the biochemical function of an essential pectin methylesterase in the gut microbe Bacteroides thetaiotaomicron.
in The Journal of biological chemistry
Demus D
(2021)
Interlaboratory evaluation of plasma N-glycan antennary fucosylation as a clinical biomarker for HNF1A-MODY using liquid chromatography methods.
in Glycoconjugate journal
CAZypedia Consortium
(2018)
Ten years of CAZypedia: a living encyclopedia of carbohydrate-active enzymes.
in Glycobiology
Description | We have identified and characterised novel glycoenzymes of interest for a range of industrial applications. These include numerous fucosidases which are enzymes catalysing the hydrolysis of fucose from a glycoconjugate. We identified and characterised a fucosidase with the capacity to specific recognise antennary fucosylation and without the need to remove sialic acid (Wu et al. Cell Mol Life Sci. 2021). Together with our industrial collaborators on the project, the enzyme has been used as part of a diagnostic assay to identify patients with a rare form of diabetes (HNF1A-MODY) . Individuals carrying damaging variants in HNF1A show decreased levels of a1-3,4 fucosylation, as demonstrated on antennary fucosylation of blood plasma N-glycans. The enzyme was first used in a novel LC-based workflow to analyse blood plasma N-glycan fucosylation as a diagnostic of patients with diabetes with clinical features matching those at risk of HNF1A-MODY (Demus et al Glycoconj J. 2021). It was then included in a high-throughput exoglycosidase plate-based assay to measure a1-3,4 fucosylation levels in blood plasma samples (Demus et al. Glycobiology 2021). We have also identified a beta-galactosidase with specificity for blood group A antigen (Wu et al Plos Biol 2021). Blood group antigens can play a direct role in infection by serving as receptors and/or coreceptors for microorganisms, parasites, and viruses including SARS-CoV-2 infection. The specificity of RgGH98 for blood group A antigen could therefore have potential application for diagnostics or therapeutics. |
Exploitation Route | The glycoenzymes could be used as tools for glycan synthesis The glycoenzymes could be used as tools for glycan profiling The glycoenzymes could be used as tools for diagnosis The glycoenzymes could be used as tools for therapeutics |
Sectors | Agriculture Food and Drink Pharmaceuticals and Medical Biotechnology |
URL | https://quadram.ac.uk/sweet-enzymes-from-gut-bacteria-discovery-to-diagnostics/https://quadram.ac.uk/link-between-the-gut-microbiome-and-blood-groups/ |
Description | One of the glycoenymes identified in this project is part of a license agreement with an industry leader specialised in glycoanalytical technology to support biopharmaceutical realisation and translational medicine. The enzyme is to be commercialised as stand-alone and as part of a diagnostic kit. |
First Year Of Impact | 2020 |
Sector | Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology |
Impact Types | Societal Economic |
Description | BSAC grant programme- COVID-19 Focussed Call 2020 |
Amount | £25,000 (GBP) |
Organisation | British Society for Antimicrobial Chemotherapy |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2020 |
End | 08/2021 |
Description | Carbohydrate analysis |
Organisation | John Innes Centre |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Supervised and coordinated research project |
Collaborator Contribution | Provided expertise and access to NMR facility |
Impact | WO2017134466A1. Patent Application on intramolecular trans-sialidase; Carbohydr Res. 2017 Nov 8;451:110-117. doi: 10.1016/j.carres.2017.08.008. |
Start Year | 2007 |
Description | Diagnostic company |
Organisation | Ludger Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | Identified and characterised glycoenzyme targets |
Collaborator Contribution | Tested glycoenzymes for application in diagnostic kit |
Impact | Commercial product |
Start Year | 2016 |
Description | Fucosidase testing |
Organisation | BASF |
Country | Germany |
Sector | Private |
PI Contribution | We have produced and characterised novel fucosidases as part of the Glycoenzyme project |
Collaborator Contribution | A subset of fucosidases were provided to BASF under MTA for them to test suitability in potential applications |
Impact | Transfer of materials |
Start Year | 2017 |
Description | Fucosidase testing |
Organisation | Ludger Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | We have produced and characterized novel fucosidases as part of the Glycoenzyme project |
Collaborator Contribution | A subset of fucosiadses have been tested by Ludger for potential application |
Impact | Exchange of materials, Technical reports |
Start Year | 2016 |
Description | STD-NMR |
Organisation | University of East Anglia |
Department | Schools of Pharmacy and Medicine UEA |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We provided proteins and ligands for analysis by STD NMR to complement some of our data on mechanisms of host-bacteria interactions. This collaboration resulted in high impact joint publications led by QIB (Proc Natl Acad Sci U S A. 2018 pii: 201715016; Nat Commun. 2017 ;8(1):2196) |
Collaborator Contribution | STD- NMR analysis of proteins and ligands we provided. Some of this work led to the development of DEEP STD NMR, leading to a joint publication led by UEA (Angew Chem Int Ed Engl. 2017 56:15289-15293). |
Impact | Proc Natl Acad Sci U S A. 2018 pii: 201715016; Nat Commun. 2017 ;8(1):2196; Angew Chem Int Ed Engl. 2017 56:15289-15293 |
Start Year | 2014 |
Description | Synchrotron Oxford |
Organisation | Diamond Light Source |
Country | United Kingdom |
Sector | Private |
PI Contribution | Provided collaborator with proteins and ligands for X-ray crystallography and cryo-EM |
Collaborator Contribution | X-ray crystallography of proteins free and in complex |
Impact | Nat Commun. 2017 Dec 19;8(1):2196. doi: 10.1038/s41467-017-02109-8. |
Start Year | 2016 |
Title | Novel Glycoenzyme licensed as stand-alone or part of a diagnostic kit |
Description | We licensed a novel glycoenzyme to a company |
IP Reference | |
Protection | Trade Mark |
Year Protection Granted | 2020 |
Licensed | Commercial In Confidence |
Impact | The glycoenzyme has been used as part of a diagnostic kit |
Description | Glycobiology Network Latin America |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Workshop on Glycobiology of host-microbe interactions in the gut. Biotechnology and glycobiology tools for human health, Guanajuato, Mexico, 9-11/10/2017 |
Year(s) Of Engagement Activity | 2017 |
Description | IBCarb |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | Contributed to the final IBCarb workshop Glycobiotechnology 2018. IBCarb (Glycoscience Tools for Biotechnology and Bioenergy) is a growing network of glycoscientists from academia and industry. IBCarb was one of the Networks in Industrial Biotechnology and Bioenergy funded by the BBSRC. The workshop was very successful and attracted around 150 attendees (international audience from academia and industry) . This was an opportunity to showcase the Glycosciences carried out in the UK and in partnership with industrial/business partners. |
Year(s) Of Engagement Activity | 2018 |
URL | https://ibcarb.com/events/ |