Community Research and Development Information Service - CORDIS

Metagenomics for the discovery of biocatalytic enzymes

Biocatalysis employs natural catalysts such as enzymes to perform chemical transformations on organic compounds. A European project aimed to obtain and characterise new biocatalysts from thermophilic bacteria.
Metagenomics for the discovery of biocatalytic enzymes
The use of biocatalytic enzymes such as transaminases (TAs) in the chemical and pharmaceutical industries has been growing in the last years. TAs catalyse the transfer of an amino group from a donor amine to an amine acceptor molecule. They represent an option for the synthesis of chiral amines, which serve as building blocks for the synthesis of different pharmaceutical compounds.

Most of the industrial processes require high temperatures. Use of thermostable enzymes would help streamline the process while avoiding energy-intensive cooling and reheating steps. The overall concept of the EU-sponsored HOTRAM (Thermostable transaminases for the synthesis of pharmaceutical building blocks) project was to discover a new generation of thermostable TAs from hot environments using metagenomics.

Metagenomics (environmental genomics or community genomics) is the study of genetic material directly recovered from the entire environmental sample.  Metagenomics is a powerful tool for enzyme discovery as it accesses the uncharacterised majority of microbes in any habitat.

During the initial part of the project, bacterial cultures were prepared from nine environmental samples collected in Iceland at temperatures ranging from 50 to 90 °C. The metagenomic DNA was extracted from samples and the corresponding expression library was constructed. The libraries were screened using the developed assays, but no positive clones were detected.

At the same time, in silico screening yielded three new TAs and the proteins were subsequently purified. The activity of these enzymes was evaluated at different temperatures using spectrophotometric assays.

New thermostable TAs with broad substrate specificity were successfully discovered and tested for the synthesis of chiral amines on an industrial scale. Importantly, the outcome of the project has a strong environmental impact as the current production of chiral amines involves polluting substances, i.e. metal catalysts. The introduction of biocatalytic methods could help reduce the environmental impact of synthetic processes in industry.

Related information


Metagenomics, biocatalysis, transaminase, thermostable enzymes, HOTRAM
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