IN SILICO RATIONAL ENGINEERING OF NOVEL ENZYMES IRENE HNL: Hydroxy Nitrile Lyase catalyzes the hydrolysis of C-CN bonds
IRENE >>Concept and objectives

Concept and objectives

Enzymes are increasingly used to perform a range of chemical reactions. These catalysts from nature are sustainable, selective and efficient, and offer a variety of benefits such as environmentally friendly manufacturing processes, reduced use of solvents, lower energy requirement, high atom efficiency and reduced cost.
However, natural biocatalysts are often not optimally suited for industrial applications. To boost the use of enzymes in industrial processes, it is important to expand the range of reactions catalyzed by enzymes and to improve their properties for industrial applications. Therefore in the last years a lot of efforts have been made for developing techniques and strategies for conferring new properties to enzymes, thus making them more suitable for applications at industrial scale. Over the past twenty years, protein engineering has contributed significantly to our understanding of enzyme catalysis, and has led to the development of enzyme variants with modified properties for synthetic transformations. Molecular modelling was used as a complementary tool to understand and to optimize enzyme-substrate interactions, as well as the enzymatic catalytic machinery.
As an alternative approach, enzyme properties can be tailored by in vitro-directed evolution of enzymes using random genetic mutation and recombination, followed by screening or selection for a desired enzymatic activity. This technique does not require a priori knowledge of the relationship between protein structure and function for experimental design.
Overall Concept
IRENE project is aimed at the development of computational methods and strategies that will enable to rationally design and produce the next generation of efficient biocatalysts for industrial applications. This will foster the diffusion of sustainable biocatalytic processes in industry. This will contribute to build on Europe’s strong position in enzyme manufacturing and utilization to attain leadership in industrial biotechnology.
Due to the strong interaction between theoretical groups and experimentalists all computational tools used in this project will be validated by experiments. Failures and successes will be used for methods’ evaluation, correction, tuning, comparison and combination, in an iterative process that will finally lead to the development of new methods and strategies, but also to the definition of practical guidelines, for any specific enzyme design issue.
According to a recent survey among industry experts in the field of biocatalysis, the major bottlenecks for replacement of conventional synthetic routes with biocatalysts in industry and to the full exploitation of enzymes’ catalytic potential can be identified in the following points:
  • requirement of multidisciplinary expertise for the implementation of the whole process, which cannot be afforded by most part of small and medium size enterprises
  • longer time for new process development
  • the still highly empirical nature of catalyst selection.
IRENE project will aim at overcoming these bottlenecks by the convergence of different expertise which ultimately will lead to a user-friendly computational platform of tools able to face 4 main tasks:
  • fast rational design of efficient biocatalysts to be produced through engineering
  • fast and efficient in silico screening of available enzymes/mutants to fully exploit catalytic potential of existing biocatalysts and providing quantitative parameters describing enzyme’s efficiency
  • fast substrate-screening and rational substrate engineering
  • understanding molecular basis of biocatalyst’ action and properties
IRENE will pursue these objectives by:
  • taking advantage of computational strategies used in different disciplines and integrate them in a unified concept for studying enzyme catalysis.
  • creating synergies and complementarities between experimental and computational approaches in order to transform information into knowledge.

Objectives will be pursued by a consortium that is funded on the combination of robust multidiciplinary expertise from EU and Russia. The consortium Beneficiaries have leading experience in enzyme design and production at industrial level (NZ), in the rational re-design of enzyme structure (KTH), in the development of different in silico methods (UCPH, MSU, MLT) and their application/adaptation to specific problems of biocatalysis (NZ, UNITS, KTH, MSU, PNPI, IBCH). Moreover the Beneficiaries have a long term experience in biocatalytic process design and application (MSU, UNITS, TUD, NUU, BIOTIR) and molecular biology (TUD, MSU, IBCH, PNPI, NUU, NZ).
More details are available in the project summary section
IRENE is a project funded by the European Commission under the Seventh Framework Programme
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