Natural products (NPs) are small metabolites of highly diverse chemical structures that are often difficult or infeasible to synthesize chemically. NPs have a wide range of applications globally including pharmaceuticals (e.g. antimicrobials, anticancer drugs), nutraceuticals, food and feed additives, flavouring, pigments, biomaterials, cosmetics and personal care products. Having access to new antimicrobial NPs is even more pertinent for addressing the current global crisis in antimicrobial resistance (AMR). A major hindrance to large-scale implementation of NPs are low yields from natural resources such as plants or animals often leading to insufficient supplies and high costs. Detailed DNA analysis of microbial genomes has shown that microbes are an underexplored, rich source of novel NPs through the identification of hundreds of thousands of Biosynthetic Gene Clusters (BGCs) encoding for the biosynthesis of NPs.
Despite recent major advances, the tool kit for handling these genes in ‘non-standard’ microbes is still too limited and resource-intensive for further manipulation. Having only a few marker genes available to use as selection system is also restricting developments. Large BGC collections exists across the world, however it proves too unwieldy and too costly to re-engineer these systems to start producing and screening the much needed novel antimicrobials.
The studentship aims to utilise naturally occurring splitters and joining systems, so-called inteins, that allow the bringing together of split marker proteins for selection. A collection of alternative units enabling moving and replication into different hosts will also be designed and genetically engineered as compatible modules. The new genetic technologies together will enable access and unlocking of NPs, thereby offering a cheaper and faster system enabling production and activity testing of NP collections that are now hard to access.
This is a SWBio DTP funded project. For guidance on how to make an application, please see: https://www.bristol.ac.uk/study/postgraduate/apply/start-application/
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