Deciphering the biosynthesis of bioactive meroterpenoids

Natural products from plants and microorganisms have been used as sources of drugs for millennia, but many of them must be modified via chemical synthesis to improve their drug-like properties. Understanding the natural products biosynthesis makes it possible to generate improved analogues by specifically changing genes involved in this process, circumventing the need for chemical synthesis. To achieve this goal, it is necessary to precisely understand the roles of different biosynthetic genes and their protein products play in the process of making the natural product. We have recently cloned the genes for the biosynthesis of bioactive meroterpenoids, natural products with cytotoxic and antibacterial activities, which hold promise for anti-cancer and anti-infective drugs development. In this project we aim to elucidate a complete biosynthetic pathway for meroterpenoids by a complex approach, which includes gene inactivation, synthesis of precursors and their use in the in vitro assays with recombinantly produced biosynthetic enzymesand producing new meroterpenoinds via biosynthetic engineering. We will test biological activities of meroterpenoid precursors and new analogues in order to evaluate their potential for further development into drugs against bacterial infections and cancer.