Michael Brigham

Exploring the role of standalone tailoring enzymes within natural product pathways

About me

I completed my MBiol and BSc in Microbiology at the University of Leeds in 2020. Throughout I particularly enjoyed bacteriology and learning about the various techniques that we use to understand cellular processes. During my MBiol project, I jumped into the world of natural product discovery and engineering, where we exploit microbes for useful, bioactive compounds. I really enjoyed the mixture of techniques that I encountered, such as microbiology, molecular engineering and bioinformatics, and I was enticed by the possibility of helping to develop revolutionary new drugs.

My project

Bacteria can produce small bioactive compounds – natural products – which can be utilised as antibiotics, anticancer agents, and agrochemicals. A major class of these natural products are the non-ribosomal peptides (NRPs). The core peptide backbone of an NRP is produced in an assembly line manner by multimodular megaenzymes, NRP synthetases (NRPSs). Additional standalone enzymes may carry out tailoring functions, such as hydroxylation and cyclisation, that can be important for the biosynthesis and/or bioactivity of the NRP. However, these standalone enzymes are not as well characterised compared to NRPSs within the context of NRP synthesis. For example, the substrate specificity of standalone tailoring enzymes is harder to bioinformatically predict compared to the modules of NRPS enzymes. This holds back our ability to make rational choices during bioengineering of NRP pathways to create novel NRPs. During my project, I aim to characterise standalone tailoring enzymes in order to define the biosynthetic logic of certain types of standalone tailoring enzymes, such as the α-ketoglutarate dependent dioxygenases, and apply this logic to creating bioengineered NRPs.


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