Manipulating bacteria for the discovery of new antimicrobials: Karen Chan

Antimicrobial resistance is one of the biggest threats to humanity globally. An increasing number of infectious diseases are becoming more difficult to treat and time is running out.

Unfortunately, many pharmaceutical companies have reduced efforts and input of resources in antimicrobial research in favour of more profitable areas. There is an urgent need for new antimicrobials and it is essential to furthering the discovery and development process via multidisciplinary approaches.

Microorganisms adapt to interact with each other and their environment through the release of metabolites for defense, regulation and communication purposes, to increase their competitiveness and chances of survival. Many of the most bioactive and clinically important metabolites including the antibiotic erythromycin, the antiparasitic avermectin and the immunosuppressant rapamycin are made in bacteria by giant ‘assembly-line’ enzymes called polyketide synthases. In contrast to drug lead libraries generated based solely on chemical methods, these bacterial metabolites are naturally selected by evolutionary pressure to effectively interact with specific biological targets. Enzymatic reactions catalysed by polyketide synthases are also capable of assembling complex molecules that is often difficult and costly to obtain via total chemical synthesis, demonstrating attractive potential for sustainable drug and agrochemical development.

In this talk, Karen focuses on how are antibiotics and other bioactive molecules made by the giant ‘assembly-line’ enzymes, polyketide synthases in bacteria and how these enzymes may be manipulated via genetic engineering for the generation of novel drugs with improved profiles.   

Slides

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Presented at Churchill College, 1 June 2016.