Bioproduction of new-to-nature molecular analogs of a potent protein kinase inhibitor of high clinical importance

Fungi are remarkably diverse and ubiquitous. Many fungal species are vital for life on our planet and some have even been domesticated as living factories to produce molecules of interest, for instance in the food and pharmaceutical industries. In contrast, fungi that thrive as pathogens pose serious medical and economic challenges. Every year, 3.75 million humans die and 125 million tonnes of the top five food crops are destroyed by fungal diseases. The available pool of antifungals is insufficient, and drug resistance has been soaring in recent years. Hence, the discovery of new antifungals and their manufacturing in cost-effective ways is in high demand. In this project, we will deploy a “good” fungus named Pichia kudriavzevii and manipulate it genetically to produce large quantities of a group of chemicals called indolocarbazoles, which we have, in recent years, been trying to advance as novel antifungal drugs to combat the “bad” fungi that cause deadly fungal infections.