Glycoenzymes for Bioindustries

Lead Research Organisation: University of Manchester
Department Name: Chemistry

Abstract

There are a wealth of glycoenzymes in nature but only a small number of enzymatic activities are used in industrial processes, primarily carbohydrate degrading enzymes used in high volume manufacturing such as amylases/xylanases/cellulases/oxidases used in baking/detergents/biofuels. Even fewer examples exist in high value manufacturing applications such as biologics: one example is the production of the therapeutic Cerezyme where alpha-neauramindase is used to deglycosylate exposing terminal Man residues improving its targeting. A major hurdle is the availability of appropriate enzymes which can limit utilisation in the early stage of process development thus reducing the number of successful processes involving glycoenzymes. The present project aims to overcome the current limitations of glycoenzyme availability by bringing together a number of innovative high-throughput approaches to biocatalyst discovery. We have assembled a list of 20 different glycoenzyme activities including various glycosyltransferases, polysaccharide-modifying enzymes, glycosidases and sugar oxidases that will form the basis of the research. Through iterative rounds of biocatalyst discovery, characterisation and development we aim to bring to market panels of different glycoenzyme classes that are readily available for screening by end users.

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.
 
Description Over 300 new glycoenzymes have been discovered and are currently under validation studies by The University of Manchester, Newcastle University, The John Innes Centre and Thye Institute of Food Research. 4 enzymes are being reviewd by Ludger Limited (UK) for us in diagnostic device testing kits.
Exploitation Route All glycoenzymes will be made available to academic and industry laboratories via Prozomix Ltd. They will make the enzymes both at small and large scale depending upon the customer requirements. The enzymes are being validated by academic laboratories and the results will be published which will benefit the research community.
Sectors Agriculture, Food and Drink,Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL http://www.glycoenzymes.com
 
Description Four glycoenzymes from this project have been sent for review and assessment by Ludger Limited (UK). Enzymes from the University of Manchester will be exploited immediately after publication by Prozomix Limited (UK).
First Year Of Impact 2016
Sector Agriculture, Food and Drink,Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description A Roadmap for Glycoscience in Europe - White Paper
Geographic Reach Europe 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact A Roadmap for Glycoscience in Europe - A joint effort between IBCarb and the EGSF this is the result of a workshop, which took place in Copenhagen in March 2014. This document outlines areas where glycoscience can address some of the challenges faced by Europe and contains recommendations for future research activities. Complementing 'Transforming Glycoscience: A Roadmap for the Future, this will be a useful document for scientists, policy makers, funding bodies and the general public alike. It has formed the basis of 'metrology of carbohydrates' event in Brussels 2016 which will lead to individual targeted white papers and EU lobbying/funding activities in the areas of health (biopharmaceuticals, diagnostics, vaccines, the human microbiome, diabetes, obseity and healthy ageing), food (soluble fibre, bet-glucans, prebiotics, high intensity sweetners), personal care and wellbing (structurants, fillers, materials, packaging - all with particular emphasis on sustainable, benign and eco-friendly materials).
URL http://ibcarb.com/wp-content/uploads/White-Paper-amended-May-15.pdf
 
Description IBCarb Director Professor Sabine Flitsch shadows an MEP
Geographic Reach Europe 
Policy Influence Type Influenced training of practitioners or researchers
Impact The IBCarb Director Professor Sabine Flitsch is participating in the MEP-Scientist Pairing Scheme and has been paired with the MEP Mairead McGuinness. The scheme aims to support the development of relationships between MEPs and scientists to improve access to scientific advice and deepen scientists' understanding of the role of science in policy-making. During a week in Brussels (25-27th January 2016), Professor Flitsch shadowed MEP McGuiness as she went about her parliamentary business, attending committee meetings and meeting officials working in key policy areas.
URL http://ibcarb.com/news/
 
Description H2020-MSCA-ITN-2015-ETN
Amount € 273,287 (EUR)
Funding ID 675671 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 11/2015 
End 10/2019
 
Title Glycoenzymes for Bioindustries 
Description Novel glycoenzymes discovered and validated 
IP Reference  
Protection Protection not required
Year Protection Granted 2017
Licensed Commercial In Confidence
Impact too early to disclose
 
Company Name Bio-Shape Ltd. 
Description Bio-Shape is a start-up company developed by academics from Manchester and Liverpool Universities to support biotechnology industries. Our purpose is to make cutting edge synthetic and analytical tools available for bioindustry needs. We have mass spectrometry based methods to analyse large and complex biomolecules with a focus on biopharmaceuticals requiring very low levels of sample material at short timescales. We develop novel biocatalysts at scale that are robust and offer a green alternative to chemical routes for industrial biotechnology and analytical applications. 
Year Established 2015 
Impact Bio-Shape is intensively research active and has been rewarded by support via numerous EU and BBSRC research grants. Bio-Shape was also a participant at the 2016 Pitch at the Palace competition.
Website http://www.bio-shape.com
 
Description BBSRC The Great British Biosciences Festival, 14-16th November 2014 
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 Professor Sabine Flitsch was successful in her bid to host "The Complex Life of Sugars" at BBSRC The Great British Biosciences Festival, 14-16th November 2014, London. The exhibition was visited by over 6,500 visitors including people from the following categories: students, teachers, public, scientists, media, potential donors/key decision makers and celebrities. One of the main exhibition activities was focused on cell surface sugars and visitors were encouraged to build a cell surface sugar and explore its interaction with cell invaders both on a cell surface and also a gold glycan array. For more contents please visit our blog http://sugar-complexity.tumblr.com/ and twitter feed @sugarcomplexity.
Year(s) Of Engagement Activity 2014
 
Description Gateways Widening Participation Event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact The activities included glycan building through arts-and-crafts, enzymatic glucose testing and a luminol demonstration, with all activities linked to the science of blood - something familiar to all the students attending. This helped high-school students to link classroom science to the real world and explore different options as a career in science. It also integrated current research topics form this project and the wider research institute.
Year(s) Of Engagement Activity 2019
 
Description Manchester Institute of Biotechnology Open Day, 8th November 2013 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact The MIB Open Day was specifically aimed at A-Level students nationally. The day focused on hands-on experiments and lectures to promote working at the interface between chemistry and biology to solve problems with a biological 'green' solution and encourage science students to pick applied science subjects. The feedback was very positive with pupils reporting that they now realized there were a lot more options for further study and jobs than they previously knew about.
Year(s) Of Engagement Activity 2013
 
Description New Scientist Live (EXCEL London) 
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 22,476 visitors, 81 pieces of news coverage, 208 journalists attended and reached 623 million people - we had visitors following up asking for resources which we have made into an activity pack for schools.
Year(s) Of Engagement Activity 2016
URL https://live.newscientist.com/
 
Description Royal Society Satellite Science Exhibition (Manchester Museum of Science and Industry) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Family friendly hands on exhibition "The Complex Life of Sugars" showcasing stands from previous Royal Society Summer Science Exhibitions, estimated attendance at the stand, over 200 people per day for 5 days
Year(s) Of Engagement Activity 2016
URL https://royalsociety.org/science-events-and-lectures/science-exhibition-manchester/
 
Description ScienceX (The Trafford Centre Manchester) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact ScienceX was part of Manchester City of Science/ESOF. We took hands on experiments including sugar building and smelling compounds in cola which can be made using biotechnology. It reached passers-by at The Trafford Centre and an audience that would not normally attend science exhibitions. The participants said that they did not like science at school and then really enjoyed the activities and discussions. It gave lots of people more confidence in their scientific abilities.
Year(s) Of Engagement Activity 2016
 
Description The Science Spectacular, Manchester Museum, 2nd November 2013 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The Royal Society Summer Science Exhibition proved so popular that we were asked to be part of The Science Spectacular, 2nd November 2013 at The Manchester Museum http://www.manchestersciencefestival.com/whatson/science-spectacular. The Science Spectacular was aimed primarily at young children and families to encourage children to enjoy science. The feedback from parents was very positive.
Year(s) Of Engagement Activity 2013
URL http://www.manchestersciencefestival.com/whatson/science-spectacular