Rational enzyme engineering to enhance the biocatalysis toolbox

It is widely recognized that the use of enzymes is a green and highly effective way of generating complex molecules such as those with chiral centers that are vital for the production of numerous pharmaceuticals and agrochemicals. However, many opportunities in this area remain underexploited. The aim of this project is to gain a detailed molecular understanding of selected biocatalysts of the transaminase (TA) and amine oxidase family in order to optimize them by protein engineering for selective chemical transformations. The hypothesis is that these enzymes are highly amenable for engineering approaches to tailor amination and oxidation reactions and that these functionalities can be combined in cascade reactions. Rational design approaches will be used to improve the properties of a selection of TAs. We will employ a combination of computational approaches and protein X-ray crystallography to gain insights into the enzymes structures and their interaction with substrates. Detailed experimental molecular insights together with MD simulations and docking approaches will allow us to rationally introduce mutations to enhance desired properties such as performance, substrate range, stability or the creation of novel functionalities. We then plan to create biocatalytic cascade reactions using combinations of our tailor-made enzymes. The obtained knowledge will enable us to generate novel proteins with improved properties for use in single and cascade transformations to produce desirable building blocks for valuable pharmaceutical and other industrial compounds.