We are interested in combining synthetic and biosynthetic tools towards the generation and identification of bioactive molecules from natural product and ‘natural product-like’ scaffolds. Our research involves the design and development of novel strategies to direct the assembly and functional diversification of biologically relevant organic skeletons.

One area of interest focuses on combining enzymatic catalysis with chemical synthesis to afford chemical transformations on complex organic scaffolds that would be very difficult to achieve by either of these methods alone. One such transformation is fluorination. H→F substitutions can have a profound impact on the pharmacokinetic profile, metabolic stability, and receptor-binding properties of drugs and lead compounds. We aim at overcoming the limitations of the traditional synthetic methods through the development of concise strategies to incorporate fluorine atoms in organic molecules in a selective manner and using mild reaction conditions.

Another area of interest is concerned with the creation of ‘designed multi-enzyme pathways’ for organic molecule synthesis in microbial hosts. In particular, we seek to develop versatile biosynthetic platforms whose chemical output can be programmed and fine-tuned in a predictive manner. To create these systems, we explore and expand the synthetic potential of naturally-occurring enzymes using a combination of synthetic and protein engineering methods. A first application of our approach is towards the development of ‘minimalistic’ versions of the natural biosynthetic routes that lead to the formation of secondary metabolites of medical interest. We also seek to adapt these artificial pathways to generate novel organic skeletons which could lead to the discovery of new classes of bioactive ‘unnatural products’.

To achieve these goals, members of the Fasan group apply concepts and methods from a variety of disciplines including chemistry, biochemistry, biomolecular engineering, and biophysics.