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
 
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 09/2020 
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
 
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/