Development of Biocatalytic Strategies for the Synthesis of Chiral Thiols and Thioethers

Active pharmaceutical ingredients (APIs) are crucial for public health. However, their synthesis is often challenging due to the high complexity of modern drug molecules.

In particular, APIs need to have well-defined chirality as opposite enantiomers can have dramatically different biological effects.

Yet, the synthesis of chiral centres is often challenging and toxic metals as well as harsh reaction conditions are often required.

Enzymes on the other hand can often achieve unmatched enantioselectivities while also avoiding such environmentally unfavourable conditions.

While several biocatalytic strategies for the synthesis of chiral alcohols and amines, have been developed few such strategies exist for the synthesis of chiral thiols and thioethers, despite 20% of all APIs containing sulfur.

In the project described herein, I will be developing biocatalytic approaches for the synthesis of thiols and thioethers by exploring promiscuous activities of classes of enzymes widely used in industry.

This will expand the tools available for their synthesis and open up new routes and new chemical space for the synthesis of APIs, and improve the sustainability.

While working with Dr Caroline Paul in the Biocatalysis group at TU Delft, I will receive training in handling nicotinamide- and flavin-dependent oxidoreductase enzymes as well as specialist computational tools for enzyme engineering, while providing my experience in high-throughput screening and chemical synthesis.

I will have the opportunity to co-supervise Bachelor, Master, and PhD students, and attend several key conferences.

This will allow me to further develop the necessary scientific and teaching skills that are required for leading my own research group.