07/21/2014

"Enzyme Google" enables search for new enzyme functions



A new search engine, including database with more than 100.000 proteins opens up totally new possibilities in the search for new enzyme functions. This "Catalophor system" is patented.

Enzymes are gaining importance as environmentally friendly, important components of industrial processes in the pharmaceutical and chemical industry. As high-precision miniature tools from nature they can solve certain tasks perfectly. The search for industrial usable enzyme functions was previously extremely complex and subjected to restrictions. A project of the Austrian Centre of Industrial Biotechnology (acib) and the University of Graz opens up a new approach in the search of new enzyme functionionalities. The structural biology research group led by Prof. Karl Gruber has developed the "Catalophor system" - a combination of database and search engine - that filters the desired enzyme functions out of tens of thousands of structure data and can even track functionalities that have not yet been discovered yet.

The procedure is similar to a Google search, although the input of data is a bit more complicated. All starts with the question for the required enzyme function. "We focus on the active site of this enzyme and write a program which specifies the positions and distances of the most important amino acids as well as important structural features in the vicinity of the active site," explains acib researcher Christian Gruber.

On the basis of this script the Catalophor system browses approximately 100,000 database entries for similarities. The result is a weighted list of possible candidates that is verified by the researchers - based on their enzymological knowledge. In the next step the most promising candidates are biotechnologically manufactured and tested experimentally in the lab. The preliminary work on the computer saves a countless experiments and screenings for new enzyme functionality.

The Catalophor system has enormous demands on the computational performance as enzyme structures are yet highly complex. For the calculations, the researchers set up a computer cluster with more than 400 cores. This also contains the database that is constantly being expanded. "Every week about 150 new structures are added," says Georg Steinkellner from acib, "our system extends itself automatically and searches for new enzyme structures in publicly accessible databases. We also refine the entire system to answer more complex search queries". The innovative method combines bioinformatics - creating the database and establishing the search engine - with a bioscience - namely programming the query based on the complex reaction mechanism of enzymes.

High practical value

The Catalophor system has a high practical benefits for science and industry. "Based on the protein structures we can discover new possible reaction pathways of enzymes that have not been described yet. For the chemical industry this approach opens up new reaction pathways that were not possible yet," says Prof. Karl Gruber. The opportunity to replace conventional industrial synthesis processes with environmentally friendly, enzymatic methods increases.

Chiral molecules are of particular importance for the chemical industry, adds Christian Gruber. These exist in two very similar shapes - as image and mirror image. Both act extremely different biologically. The Catalophor system can detect enzymes to produce both variants of chiral molecules in their pure form. And it can offer alternatives to patented enzymes.

» Original publication

Source: Austrian Centre of Industrial Biotechnology (ACIB)