Total Biosynthesis: A Highly Efficient Strategy to Bioactive Azaphilones

• Applicant: Professor Dr. Russell J. Cox
• Subject Area: Biological and Biomimetic Chemistry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 549520638

The urgent requirement to decarbonize all aspects of the economy means that bioactive small molecules should be produced in as few steps as possible - ideally by a single step. Total chemical synthesis of small molecules is inherently step- (and carbon) intensive, but it is highly flexible and predictable. On the other hand, total biosynthesis - the production of bioactive compounds using native biological pathways - is highly efficient and inherently sustainable. However, total biosynthesis lacks flexibility, being able to make known compounds with ease, but much less able to make new compounds. This project focusses on ways to expand the flexibility of total biosynthesis within the arena of bioactive azaphilones. The aim is to set up mix-and-match expression vectors that can be combined like chemical regents for the programmed production of a large range of related bioactive azaphilones in single step procedures. The bioactive compounds will be exploited in collaborations in the area of structural biology because their target, ACE2, is the key route by which the SARS-COV2 virus enters mammalian epithelial cells. The compounds are also known to be potent inhibitors of bacterial biofilm formation and collaborations will expand knowledge in this area.

• DFG Programme: Research Grants