Drug design and protein engineering of a new class of enzymes

Mycobacterial pathogens are the causative agents of diseases such as tuberculosis, leprosy and Buruli ulcer and are a major threat to human health. A newly discovered family of F420H2-dependent reductases (FDRs), which utilize a co-factor (F420H2) that is not found in humans, has been shown to contribute to mycobacterial virulence. However, FDRs are also an Achilles heel; their absence in humans has led to the discovery of antibiotics that are specifically ‘activated’ by FDRs, making them toxic to bacteria but not humans. Mycobacterial pathogens are also a valuable resource for biotechnology. Recent work has shown that FDRs also have a remarkable capacity to degrade a wide range of food toxins and environmental pollutants such as aflatoxins, dyes, explosives and byproducts of diesel combustion. This project aims to solve the molecular structures of FDRs from important mycobacterial pathogens. These structures will then be used for drug design and protein engineering experiments to produce improved antibiotics and designer enzymes to protect the health and environment of Australians.

Potential Projects:

(1) Structural characterization of FDRs from mycobacterial pathogens.

(2) Fragment-based drug design.

(3) Engineering FDRs for biotechnology.