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Building a synthetic biology pipeline to develop nucleoside therapeutics

24 months
Approved budget:
Dr Alistair Brown
Professor David Ackerley
Dr Lawrence Harris
Associate Professor Robert Keyzers
Health issue:
Infectious disease
Proposal type:
Emerging Researcher First Grant
Lay summary
This project seeks to develop a synthetic biology platform that combines discovery and sustainable production of novel nucleoside analogues, to combat bacterial and viral infections. Nucleoside analogues can be powerful drugs, like Merck’s molnupiravir (Covid19) or NZ’s own mundesine (T-cell lymphoma), but some classes are hard to access using traditional chemistry. I have developed a laboratory strain of Escherichia coli bacteria that can synthesise minimycin, a minimal nucleoside analogue with strong metabolic stability and potent antimicrobial and anti-cancer properties. By leveraging my serendipitous experience with a gene now known to govern nucleobase synthesis, I have mined DNA databases for associated genes that ‘decorate’ the core minimycin structure with different functional groups. I will add these genes individually and in combinations and test the resulting nucleoside analogues to identify promising new drug leads. This work will help me foster collaborations, generate new IP, and build an independent research career.