Catalyst for metagenomics

Almac lands new metagenomics and enzyme discovery program with University College London

Lloyd Dunlap
CRAIGAVON, U.K.—The Almac biocatalysis group has secured aBiotechnology and Biological Sciences Research Council (BBSRC) program withUniversity College London (UCL) focused specifically on metagenomics and novelenzyme discovery.
R&D will be carried out jointly by Almac and thedepartments of biochemical engineering and chemistry at UCL, with high-level inputfrom Profs. John Ward and Helen Hailes, who are described as "two world leadersin the field of biocatalyst discovery and application," in the releaseannouncing the collaboration.
 
Metagenomics isthe study of genetic materialrecovered directly from environmental samples. Because of its ability to reveal the previouslyhidden diversity of microscopic life, metagenomics offers a powerful lens forviewing the microbial world.
 
"This clearly adds further depth to our expertise," says Dr. Tom Moody, Almac'shead of biocatalysis and isotope chemistry. "This collaboration has come at the right time, as more and morecustomers need scalable green technologies to access difficult-to-make chiralchemicals. Having access to the right enzymes today will drive 'hit toprocess.' The introduction of enzymes into processes earlier in the drugdiscovery pipeline will therefore help to drive cost down as the projects moveforward."
 
Moodyexplains how the collaboration will proceed: Research at UCL will preparemetagenomic DNA, perform the bioinformatics and enzyme searches and identifylists of potentially interesting and useful enzymes. These will then beselected by Almac, and after primer design, cloning and over-expression of theenzymes at UCL, they will be screened at UCL and Almac against small-compoundlibraries. Almac will select the enzymes and the assessment of the enzymes by in-silico methodology when large numbers of aparticular class of enzyme are identified. Almac will also assist with novelenzyme assays, substrate selection and biocatalytic scale-up. Hit enzymes willthen move from UCL into Almac for further evolution and commercialization.
 
According to Almac, the application of biocatalysistechnology to the pharmaceutical and fine chemical industries is continuing togrow year over year, and this trend is mirrored in the increasing number ofsynthetic projects being carried out by the biocatalysis group at Almac. Theonly limitation of biocatalysis is in the number of diverse enzymes availablein a given enzyme class, which dictates both the substrate range and thestereoselectivity observed for a desired chemical transformation. The majorityof enzymes used in biocatalysis are derived from microbial sources. However, itis 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 toextract the total DNA from an environment, can circumvent this problem and allowaccess of as much as 99 percent of enzyme genes present in environmentalsamples.
 
"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 willmainly focus on transaminase and cytochrome P450s enzymes. We will identify,clone and express these enzymes before carrying out extensive screening againstpanels of 'typical' pharmaceutical and fine chemical substrates. This shouldenable us to identify novel and commercially useful enzyme biocatalysts. As thefollow-on step, directed evolution at Almac will enable further development ofthe lead enzymes concerned."
 
 
The Almac Group provides a broad range of services fromR&D, biomarker discovery and development, API manufacture, formulationdevelopment, clinical trial supply and commercial-scale manufacture. Almacprovides services to more than 600 companies, including world leaders in thepharmaceutical and biotech sectors. The company employs more than 3,300individuals and has U.S. operations in Pennsylvania, North Carolina andCalifornia.

Lloyd Dunlap

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