Biosynthesis and mode of action of a new antifungal antibiotic produced by bacterial plant pathogens and rhizosphere bacteria

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The global human population is increasing and it is estimated to reach around 9 Billion by mid-century. Demand for human and animal food crops will increase in line with this growth rate and our food security will be compromised unless we can significantly increase crop productivity, decrease crop losses due to disease and spoilage - or, preferably, both. Recent research has shown that fungal (and oomycete) plant pathogens play increasingly important roles in causing plant diseases that reduce crop production or lead to spoilage of harvested food crops. Current crop protection methods involve various approaches, including the use of some pesticides made by polluting chemistry that can have undesirable environmental impacts.This project will involve a study of a novel antifungal molecule(s) that is made naturally by some species of bacteria that live in close association with plants. This naturally-made antifungal antibiotic is lethal to a range of fungi that kill pants, including crop plants, and so it might be useful in preventing or limiting crop diseases without recourse to synthetic toxic pesticides. The genes responsible for the formation of this new natural antifungal molecule have been discovered in a range of bacteria isolated from the environment and a hypothetical pathway to biosynthesis of the active molecule has been suggested. We will overproduce this new molecule using bacterial genetics and physiology methods and then purify the antifungal to try to determine the chemical structure of the antibiotic using a range of chemical and physical methods. We will study how the new antibiotic is assembled in the bacteria that produce it. We have shown that the antifungal antibiotic can also kill simple yeast (fission yeast) in addition to fungi that cause plant disease. The simple yeast is easy to study using genetics and molecular biology methods and so we intend to exploit this by investigating the cellular target of the new antifungal in yeast cells. We expect this information will be also directly relevant to identifying the nature of the molecular target in the plant pathogenic fungi and this will help us in future to develop different natural and semi-synthetic molecules that may protect crop plants from disease and spoilage - and thereby enhance our food security.