Almac secures new discovery programme with UCL

BBRSC programme combines chemistry and biochemical engineering at UCL with Almac’s biocatalysis group

The Almac biocatalysis group has secured a prestigious Biotechnology and Biological Sciences Research Council (BBSRC) programme with UCL focused specifically on metagenomics and novel enzyme discovery. The R&D work concerned is set to be carried out jointly between Almac and the departments of Biochemical Engineering and Chemistry at UCL, with high level input from two world leaders in the field of biocatalyst discovery and application, Professors John Ward and Helen Hailes.

The application of biocatalysis technology to the pharmaceutical and fine chemical industries is continuing to grow year-on-year and this trend is mirrored in the increasing number of synthetic projects being carried out by the biocatalysis group in Almac.

The only limitation of biocatalysis is in the number of diverse enzymes available in a given enzyme class, which dictates both the substrate range and the stereoselectivity observed for a desired chemical transformation. The majority of enzymes used in biocatalysis are derived from microbial sources. However, it is known that only a tiny percentage (as low as 0.1% from soil samples) of bacteria present in an environmental sample can be cultured and isolated.

Metagenomics, a culture-independent technique used to extract the total DNA from an environment, can circumvent this problem and allow access up to 99% of enzyme genes present in environmental samples. Work previously carried out at UCL has allowed a series of metagenomes to be obtained from various unusual sources. The use of bioinformatic tools developed by John Ward with Prof Christine Orengo of the Structural and Molecular Biology department at UCL will allow the metagenomes concerned to be mined for enzymes usable in both synthetic chemistry and synthetic biology projects.

The need for more diverse enzymes has never been greater

‘The need for more diverse enzymes has never been greater and this research programme further emphasises Almac’s commitment to UK research and to biocatalysis development,’ said Dr Tom Moody, Almac’s Head of Biocatalysis & Isotope Chemistry. ‘This clearly adds further depth to our expertise and complements our recent collaboration with DSM in accessing diverse enzyme collections,’.

Professor Ward remarked: ‘We are very excited to continue working with Almac on this prestigious project, building on many years of collaboration and partnership. Indeed, this project will see our internal capabilities further developed with true industrial needs in our vision.’

According to Moody, the project will mainly focus on transaminase and cytochrome P450s enzymes. ‘We will identify, clone and express these enzymes before carrying out extensive screening against panels of ‘typical’ pharmaceutical and fine chemical substrates,’ he said. ‘This should enable us to identify novel and commercially useful enzyme biocatalysts.

‘As the follow-on step, directed evolution at Almac will enable further development of the lead enzymes concerned.’

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