PhD project title

Overcoming Enzyme Poisoning in Bioprocesses

Outline description, including interdisciplinary, intersectoral and international dimensions (300 words max)

Pharmaceutical companies rely heavily on bioprocesses for the manufacture of many of their active ingredients due to environmental, safety and cost factors. Almac Sciences is a world leader in biocatalysis, and is engaged in the development, application and global supply of enzymes for chemicals manufacture.

When removed from its natural environment the performance of an enzyme can become compromised due to stability issues in the presence of chemicals. Many chemicals can affect enzyme activity irreversibly and “poison” the enzyme. Drug companies need to engineer stability into the enzyme at the protein level or protect the enzyme from these poisons during the bioprocess. This project will focus on the later.

Collaborations have been established with Prof. Paul Kamer at Leibniz Institute for Catalysis (LIKAT), Rostock, Germany in order to prepare artificial enzymes [1] and with Almac Sciences to access engineered enzymes.

The student will work with these enzymes and devise new methods of avoiding poisoning. Material and solvent technologies will be investigated to protect and stabilise the enzyme. The project will combine chemistry, biology, materials and industrial expertise. Marr has developed solvents that sit above a biocatalytic reaction and remove the so-called poisons, thereby increasing productivity of the processes.  In collaboration with Dr Patricia Marr, materials will be made to encapsulate enzymes in protective semi-permeable materials, and gels will be used that absorb poisons or selectively release substrates. The project will result in new methodology to support and stabilise enzymes for chemical processing.

[1] Catalytic and biophysical investigation of rhodium hydroformylase. H. T. Imam, A. G. Jarvis, V. Celorrio, I. Baig, C. C. R. Allen, A. C. Marr, P. C. J. Kamer. Catal. Sci. Technol., 2019, 9, 6428-6437. 2019 Catalysis Science & Technology HOT Article

Key words/descriptors

Biocatalysis, Pharmaceuticals, Bioprocesses, Enzymes, Materials, Solvents

Fit to CITI-GENS theme(s)

• Information Technology,
• Advanced Manufacturing,
• Life Sciences
• Creative Industries.

Supervisor Information

First Supervisor:      Dr. Andrew C. Marr                                                             School: Chemistry and Chemical Engineering

Second Supervisor: Prof. Christopher Allen                                                       School: Biological Sciences

Third Supervisor:  :  Prof. Tom Moody  & Dr. Stefan Mix                                Company: Almac

Tom Moody is Vice President of Technology Development and Commercialisation, Stefan Mix is Head of Biocatalysis.

Name of non-HEI partner(s)

Almac (and Leibniz Institute for Catalysis)

Contribution of non-HEI partner(s) to the project:

The input of Almac is central to the project. Almac will provide consultation on the latest techniques and enzyme classes being used by drug and drug intermediates manufacturers and will highlight the main problems, bottlenecks and poisons. They will ensure that the technologies investigated are realistic in an industrial context. In addition Almac will provide materials and techniques. The most valuable of the materials will be enzymes, which would normally be too expensive for projects of this nature. Techniques provided will include industrial assays of enzyme activity, and this will enable the student to directly compare their systems with industrial standards. Almac will also offer secondments to Almac laboratories to receive training in the area of bioprocessing. Almac will also ring fence kilo batch reactors to test the developed technology at pilot scale with the associated training for the student.

Prof Tom Moody and Dr Stefan Mix have >100 publications in the area of bioprocessing and have taken bioprocesses from mg scale right through to production multi-tonne manufacture. Almac was 19^th in Belfast Telegraph’s Northern Ireland’s top 100 companies 2019 and is the leading pharmaceuticals company in N.I. Almac is committed to grow in N.I. and is well positioned to implement these technologies at commercial scale. New technologies are of strategic importance to the future growth of chemical manufacturing in the UK and Europe. Growth will require highly skilled graduates with an understanding of chemistry and biology, and more specifically a working understanding of proteins, biocatalysts and bioprocesses.  This project is a perfect fit to attract and train such individuals.

LIKAT is a leading research-only institute in catalysis and will provide time from Prof. Kamer and members of his team, infrastructure costs and analytics. The PhD student will also go on placement to Germany.

Research centre / School

Chemistry and Chemical Engineering

Subject area

Organic Synthesis and Chemical Biology, Biocatalysis and Bioprocessing