Production, characterization, and engineering of yanuthone and novel antimicrobial agents to combat antimicrobial resistance (AMR)

The loom of antimicrobial resistance is a well-publicised crisis, one of the top 10 global public health threats facing humanity, with 10 million deaths per year predicted by 2050; equating to 1 death per 3 seconds – more than current cancer mortality. Thus, highlighting the desperate need to produce new antimicrobial medicines that can impact drug resistance, improve human health, and save lives. 

A recently discovered antimicrobial called yanuthone (structurally different to most existing antibiotics) has been found to be effective against the superbug MRSA (methicillin-resistant Staphylococcus aureus) and other human disease-causing pathogens. The production of the yanuthone antimicrobial occurs naturally in a common fungus and involves a pathway of several enzymes (nature’s catalysts) that build the drug in a stepwise manner from a central core, adding on constituents that give the antibiotic its unique properties. The characterization of several of these enzymes with allowing their engineering to change the way they construct the antimicrobials and produce new derivatives

This PhD project involves the initial biochemical characterisation and subsequent engineering of proteins involved in the latter stages of yanuthone production, aiming to produce new yanuthone derivatives with enhanced antimicrobial activity.

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