Extra Seminar Rosalind Franklin Fellowship

Speaker:       Dr. Sandy Schmidt

BY THE POWER OF NATURE’S CATALYSTS

Understanding and designing enzymes for human applications

Host:             Prof. dr. M. Tromp

ABSTRACT
Biocatalysis has emerged as an environmentally friendly technology for the chemical and pharmaceutical industries. A large series of successful examples underlines that biocatalysis can improve the sustainability of chemical processes and thus complements other catalytic technologies very successfully. Natural enzymes only catalyze a fraction of the reactions that are routinely employed by synthetic chemists. Thanks to the new possibilities that opens up due to the huge “explosion” in the number of protein sequences and advanced bioinformatic tools, the creation of tailored biocatalysts has already speed-up the process of design. However, accurate predictions on the outcome of amino acid substitutions are extremely difficult due to the limited understanding of the catalytic roles of amino acids and their interaction for the mechanism. In particular, the contribution of peripheral amino acids is particularly difficult to rationalize. Our limited understanding of structure-function relationships that exist in protein catalysts makes the straightforward design rather challenging. In order to shed light on the molecular connections that defines the relation between protein structure and function, we investigate multi-component Rieske non-heme iron oxygenases, but also electron transfer pathways in ferredoxin-dependent enzymes and light-driven biocatalytic reactions. A first step in order to tackle this challenge is the deeper investigation of electron transfer pathways and oxygen tunnels in such multi-component

enzymes, which are not only, influenced by allostery, but also by protein-protein interactions with their redox partners. It is assumed that the knowledge acquired by a defined set of mutations on the surface of the redox partners will contribute to a better understanding of these effects and could thus lead to promising applications of such complex multi-component enzymes.