RedAm Detectives

Winner: 2021 Chemistry Biology Interface Division Horizon Prize:
Rita and John Cornforth Award

For the development of new biocatalysts for asymmetric reductive amination, from fundamental understanding of mechanism and structure to applications on an industrial scale.

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A partnership between the University of York, the University of Manchester, GSK and SME biotechnology company Prozomix has developed a new way to develop medicines more sustainably.

The new technology is very timely, as the global pharmaceutical industry looks to employ manufacturing processes that are sustainable. These medicines must also be produced in highly pure form for use in patients. One such approach employs enzymes or biocatalysts which are safe, highly selective and produce minimal waste.

The collaboration began with the discovery and characterization of a new type of biocatalyst by the scientific research teams at the University of Manchester and the University of York. Subsequent to their discovery, scientists at GSK spotted an opportunity to apply these new biocatalysts for a more efficient industrial process to manufacture a medicine in its oncology portfolio.

This demonstration highlights how the technology can be broadly used across drug development and represents an efficient and sustainable way to produce many lifesaving medicines. These new biocatalysts are now available from Prozomix Ltd for other groups to evaluate.

As a result of close cooperation between the partners, the time between discovery and application was less than four years.

Our number one motivator is the patient. There is no greater motivation than knowing you are helping improve the quality of patients’ lives. The technology we are applying can produce medicines in a more qualitative and efficient way and champions sustainable solutions.

The team

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G.A. Aleku, PhD Researcher, University of Manchester
Murray J.B. Brown, Scientific Leader & GSK Fellow, Synthetic Biochemistry, GSK
Sandy Chang, Investigator, Synthetic Biochemistry, GSK
Simon J. Charnock, Managing Director, Prozomix Ltd
D.J Cook, Site Manager, Prozomix Ltd
R.A.M. Duncan, Production Manager, Prozomix Ltd
James D. Finnigan, General Manager, Prozomix Ltd
Scott P. France, PhD Researcher, University of Manchester
Doug Fuerst, Director, Synthetic Biochemistry, GSK
Kirsty M. Graham, Senior Research Scientist, Prozomix Ltd
Gideon Grogan, Project Leader, Structural Biology, University of York
Rachel S. Heath, Postodoctoral Researcher, University of Manchester
Joseph Hosford, Investigator, Synthetic Biochemistry, GSK
S. Hussain, PhD Researcher, University of Manchester
Leigh-Anne F. Ihnken, MPD Leader, Synthetic Biochemistry, GSK
Druhar Khan, GSK
Ulrike Klemstein, Research Technician, University of Manchester
Jonathan Latham, Investigator, Synthetic Biochemistry, GSK
Friedemann Leipold, Postdoctoral Researcher, University of Manchester
Chris MacDermaid, Scientific Leader & GSK Associate Fellow, Protein Design and Informatics, GSK
H. Man, PhD Researcher, Structural Biology, University of York
Juan Mangas-Sanchez, Postdoctoral Researcher, University of Manchester
James R. Marshall, PhD Researcher, University of Manchester
Sarah L. Montgomery, PhD Researcher, University of Manchester
Anne A. Ollis, Investigator, Synthetic Biochemistry, GSK
Ryan B. Palmer, PhD Researcher, University of Manchester
Doru Roiban, Scientific Leader & GSK Fellow, Synthetic Biochemistry, GSK
Mahesh J. Sanganee, Investigator, Chemical Development, GSK
Markus Schober, Investigator, Synthetic Biochemistry, GSK
Mahima Sharma, Postdoctoral Researcher, Structural Biology, University of York
Thomas W. Thorpe, PhD Researcher, University of Manchester
Nicholas J. Turner, Project Leader, University of Manchester
P. Yao, Postdoctoral Researcher, University of Manchester

Q+A

Doru Roiban, Scientific Leader and Fellow at GSK

What was your role within the team?

I led the team of scientists who discovered, engineered and then applied the enzyme to improve the way the medicine was made.

What different strengths did different people bring to the team?

We were a team of diverse people, both culturally and scientifically and we all felt being part of the team with the same goals of pushing the boundaries of science and improving the way drugs are made. Everyone was empowered to speak up, shared their ideas and felt included which helped our endeavours.

What were the biggest challenges in this project?

The biggest challenge was venturing into the unknown with a new technology where you do not have a reference for the work you are doing. While at the same time needing to inspire your team and build confidence with stakeholders. But the opportunity to translate novel science into an industrial process was also one of the most exciting aspects of the project.

How are the chemical sciences making the world a better place?

The technology we are applying helps us make the product in a more sustainable and more efficient way which is essential. I’m happy to be part of the change towards GSK’s Healthy Planet, Healthy People sustainability ambitions.

What advice would you give to a young person considering a career in Chemistry?

Be curious, be innovative! Always strive to continue learning and explore opportunities and be open to possibilities. Try to constantly improve and follow the science which is something we prioritize at GSK. You can do anything if you have the passion, the focus, the drive and the support.

What inspired you and your team?

Nicholas Turner, Professor of Chemical Biology, University of Manchester

What was your role within the team?

Principal Investigator (PI) of the University of Manchester team

What was the University of Manchester’s role?

UniMan and York discovered the first example of an enzyme (reductive aminase = RedAm) capable of catalysing asymmetric reductive amination of amines with ketones and aldehydes. This discovery, together with detailed characterisation of the enzyme, led to further application by others including GSK.

How are the chemical sciences making the world a better place?

Chemistry is the only discipline that creates new molecules (e.g. pharmaceuticals, agrochemicals, polymers, materials, flavours, fragrances etc) and demonstrates the practical utility of these chemicals for applications in everyday life.

Why is chemistry important?

Chemistry helps to feed people, cure people from illness, keep people warm and clothed and improve the general quality of life of everyone globally.

Dr Doug Fuerst, Senior Director, Synthetic Biochemistry at GSK

What is next for the technology?

The work started at the University of Manchester and York by discovering new enzyme activity and what we’re now able to show is that those enzymes can be developed in a way that’s commercially and industrially relevant.
Going forward, we’re now able to apply the technology to more compounds and more challenging transformations – increasing the complexity and breadth of deployment across the pharmaceuticals industry.

Where do you see biggest impact of the technology?

In sustainability. At GSK we recently announced our corporate Healthy Planet, Healthy People sustainability goals and applying this type of technology helps us realise that vision for the future, allowing us to be more sustainable.

What’s the importance of international collaboration in the chemical sciences?

We strive to follow the science, and the best science doesn’t exist in one location. For any scientific challenges we face, we look to bring together people and skillsets no matter where they are located, and that often means building international teams to deliver our goals and objectives.