Project description

Most enzymes rely on a cofactor for their functioning. These accessory molecules or ions are essential for enabling protein-based catalysis of reactions that are crucial to life. Cofactor-dependent enzymes have evolved to efficiently capture, bind, and utilize specific cofactors for catalysis.

In this project, we will employ computational approaches to reconstruct cofactor-dependent enzymes from specific redox enzyme families. Our primary focus will be on flavin-dependent enzymes, aiming to understand how cofactor specificity and catalysis have evolved over time. In addition to using ancestral sequence reconstruction (ASR) to biochemically characterize ancestral flavoenzymes, we will also perform a comprehensive sequence and structure-based analysis. This dual approach will generate a global overview of the evolutionary pathways of certain redox enzyme families. The insights gained will be used to engineer new cofactor-dependent enzymes with enhanced or novel functionalities.

By integrating these computational methods with experimental validation, we aim to uncover the underlying principles governing enzyme evolution and cofactor-protein interaction. This knowledge will not only advance our understanding of enzyme evolvability but also enable the design of enzymes tailored for specific biotechnological applications. Ultimately, our work seeks to bridge the gap between natural enzyme evolution and the rational design of novel biocatalysts.

Additional specifications

We look for a candidate with a MSc in Biochemistry, Life Sciences or a related discipline that is keen on investigating how enzymes evolve and have evolved. Experience in enzyme characterization and/or bioinformatics (sequence/structure analysis) is recommended.