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Catalyst for metagenomics
CRAIGAVON, U.K.—The Almac biocatalysis group has secured a Biotechnology and Biological Sciences Research Council (BBSRC) program with University College London (UCL) focused specifically on metagenomics and novel enzyme discovery.
R&D will be carried out jointly by Almac and the departments of biochemical engineering and chemistry at UCL, with high-level input from Profs. John Ward and Helen Hailes, who are described as "two world leaders in the field of biocatalyst discovery and application," in the release announcing the collaboration.
Metagenomics is the study of genetic material recovered directly from environmental samples. Because of its ability to reveal the previously hidden diversity of microscopic life, metagenomics offers a powerful lens for viewing the microbial world.
"This clearly adds further depth to our expertise," says Dr. Tom Moody, Almac's head of biocatalysis and isotope chemistry. "This collaboration has come at the right time, as more and more customers need scalable green technologies to access difficult-to-make chiral chemicals. Having access to the right enzymes today will drive 'hit to process.' The introduction of enzymes into processes earlier in the drug discovery pipeline will therefore help to drive cost down as the projects move forward."
Moody explains how the collaboration will proceed: Research at UCL will prepare metagenomic DNA, perform the bioinformatics and enzyme searches and identify lists of potentially interesting and useful enzymes. These will then be selected by Almac, and after primer design, cloning and over-expression of the enzymes at UCL, they will be screened at UCL and Almac against small- compound libraries. Almac will select the enzymes and the assessment of the enzymes by in-silico methodology when large numbers of a particular class of enzyme are identified. Almac will also assist with novel enzyme assays, substrate selection and biocatalytic scale-up. Hit enzymes will then move from UCL into Almac for further evolution and commercialization.
According to Almac, the application of biocatalysis technology to the pharmaceutical and fine chemical industries is continuing to grow year over year, and this trend is mirrored in the increasing number of synthetic projects being carried out by the biocatalysis group at 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 percent 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 of as much as 99 percent of enzyme genes present in environmental samples.
"The need for more diverse enzymes has never been greater, and this research program further emphasizes Almac's commitment to U.K. research and to biocatalysis development," Moody states. "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. 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."
The Almac Group provides a broad range of services from R&D, biomarker discovery and development, API manufacture, formulation development, clinical trial supply and commercial-scale manufacture. Almac provides services to more than 600 companies, including world leaders in the pharmaceutical and biotech sectors. The company employs more than 3,300 individuals and has U.S. operations in Pennsylvania, North Carolina and California.