Grant: Alliance Grants

The global pharmaceutical industry emits more greenhouse gases than the automotive production sector as manufacturing active pharmaceutical ingredients currently relies on many energy-intensive, unsustainable chemical synthesis steps using petrochemicals-based raw materials. So far, the production of pharmaceuticals is not sustainable, as complete synthesis or semisynthetic functionalization often requires harsh and toxic chemicals derived from fossil fuels. Derivatization of natural products to diversify bioactive molecules for biological screenings by traditional chemistry is challenging, as chemical modifications are strongly restricted by the lack of selective, sustainable derivatization methods. In contrast, enzymes are valuable catalysts for promoting chemical transformations even at unactivated positions with a high degree of chemo-, regio-, and stereoselectivity and under mild reaction conditions. Here, we will employ systematic strategies to mine, discover, and fine-tune new biocatalysts for the functionalization and diversification of complex pharmaceuticals. We will develop novel catalytic systems that enable the sustainable production of new and existing therapeutic compounds with a strong focus on the enzymes cytochrome P450 monooxygenases (CYPs) and anti-cancer and anti-addiction alkaloids. This groundbreaking endeavour provides an efficient way to access current and novel drugs without relying on harsh and toxic chemical catalysis and is unique to our laboratories. The new molecules, biocatalysts and bio-platforms for pharmaceutical production will eventually help replace petrochemicals-reliant manufacturing with nature-inspired and biocatalysis-based methods, addressing the central theme in NSERC's and DFG's strategic priorities on Sustainable Processes and Novel Catalysts for Green Chemistry, and paving a way toward Canada's and Germany's goal to net zero by 2050.