Investigation of Fengycin Mechanism Using Biological, Chemical and Biophysical Tools

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Control of plant pathogens is vital for effective crop production and whilst many products currently available for the elimination of fungal pathogens are synthetic chemicals, there are some biological control products ('biofungicides'). One of these is the product Serenade, which is manufactured by the company AgraQuest. This product is a bacterium, Bacillus subtilis QST713, which produces a mixture of bioactive lipopeptides (surfactins, iturins and fengycins). It has been established that the lipopeptides target the membranes of phytopathogens and considerable research effort has enabled a deep understanding of both the biosynthesis and mechanism of action of surfactins and iturins. However, much less is known about fengycin, which is the second most abundant lipopeptide produced by the bacterium. This project aims to deepen our knowledge of the anti-fungal mechanism of fengycin and to generate new fluorinated fengycin derivatives, via a combination of synthetic chemistry and biosynthesis, with improved bioactivity. The research will build on a highly successful collaboration between researchers in Durham (Steven Cobb) and Dublin (Cormac Murphy) who have expertise in synthetic fluorine chemistry and microbial biosynthesis, respectively. The project will employ a PDRA in Durham for the synthetic and biophysical aspects of the work and a PhD student in Dublin to conduct the microbiology/molecular biology experiments. In addition the PhD student (Dublin) will work closely with colleagues in Durham's Biophysical Science Institute, which has the specialist facilities necessary to probe the interaction between the lipopeptide and membrane. This will have the added benefit for the student to gain proficiency in a range of research tools that will boost chances of subsequent employment. The research will be of significant interest to academic researchers involved in natural product biosynthesis and those investigating the antifungal action of fengycins, and to companies that commercialise lipopeptides as biocontrol agents. Furthermore, the new fluorofengycins could open possibilities in the healthcare sector for the treatment of fungal infections.