Funded Projects

Scheme

Discussion Board
password protected

Contact

 

Focus

All cellular reactions are catalysed by proteins (enzymes) or RNAs (ribozymes). Life cannot be understood without understanding how these molecular biocatalysts function and how they are stabilised. The ongoing sequencing of entire genomes and the possibilities of manipulating individual genes at will has led to important progress towards this goal, but central questions have remained open. Within the Schwerpunktprogramm (Priority Program) 1170 Directed Evolution to Optimize and Understand Molecular Biocatalysts, the novel and powerful approach of directed evolution will be used to tailor molecular biocatalysts and to gain new and crucial insights into their sequence-structure-function relationship.


Directed evolution in vitro imitates millions of years of natural evolution on the short time scale of laboratory experiments and allows to manipulate and analyse biocatalysts in a completely new fashion. In a directed evolution experiment, first large gene libraries are generated by random mutagenesis. From these libraries novel enzymes or ribozymes are isolated by elaborate screening or selection techniques, followed by their in-depth biochemical characterisation (see the scheme). In contrast to the more traditional rational design, directed evolution does not require a detailed a priori knowledge of the structure or mechanism of a biocatalyst. It is, moreover, particularly instructive because it can provide unexpected solutions that go beyond the original hypothesis.


In the Priority Program 1170 directed evolution will be used for a dual purpose: first, to modify and optimise molecular biocatalysts and, second, to approach the long-standing questions regarding the molecular basis of enzyme and ribozyme stability, function and evolution from a different perspective. To achieve these goals, the newly generated enzymes and ribozymes will be analysed by state-of-the-art tools of protein and nucleic acid chemistry, enzymology, structural biology, and theoretical chemistry. Specifically, we aim at answering the following questions:

  • What are the possibilities and where are the limits for optimising enzymes and ribozymes and for reshaping them to catalyse non-natural reactions?
  • Are there common principles among enzyme- and ribozyme-mediated catalysis?
  • How much conformational stability and flexibility is required for optimal catalysis?
  • What is the structural basis of substrate- and stereo-selectivity of molecular biocatalysts?

Answering these questions will (i) allow to produce tailored biocatalysts that will be extremely useful for both basic research and industrial applications and (ii) provide novel insights into the sequence-structure-function relationship that cannot be obtained by classical biochemical and biophysical approaches.

 

Presentations of the Regensburg Meeting,  6.3. -  8.3. 2005 (password protected)

Presentations of the Bremen Workshop,  31.7.- 2.8. 2006 (password protected)

Program of the Bad Herrenalb Meeting,  29.9. - 3.10.2007 

Program of the Regensburg Meeting,  17.9. - 20.9.2009