Nature has evolved over millions of years to produce an extraordinary diversity of natural products (NPs), which remain a unique source of inspiration for medicine and crop protection. Unlike synthetic molecules, NPs offer unmatched chemical diversity and novel scaffolds for drug discovery. However, traditional methods of isolating bioactive compounds from plants or microbes face limitations, while synthetic chemistry has failed to deliver the same level of innovation. Building on a previous SNF project that generated 189 novel NP derivatives through fungal biotransformation, this project develops a second-generation library with enhanced biological activity. Using fungal enzymes and live microorganisms, new substrates will be sustainably transformed into innovative molecules, further expanding NP diversity. All compounds will be screened for antifungal, antibacterial, antiviral, and cytotoxic activity. By combining expertise in natural product chemistry, mycology, and bioassays, the project strengthens Switzerland’s position in sustainable innovation at the interface of health, agriculture, and biotechnology.