Weekly seminar by Dr Thomas Booth: Evolution of Adenylation-Domain Specificity in Non-Ribosomal Peptide Synthesis
|Event Name||Weekly seminar by Dr Thomas Booth: Evolution of Adenylation-Domain Specificity in Non-Ribosomal Peptide Synthesis|
|Start Date||9 Jul 2019 1:00 pm|
|End Date||9 Jul 2019 2:00 pm|
Dr Thomas Booth from School of Molecular Sciences, University of Western Australia, will give a weekly seminar, Evolution of Adenylation-Domain Specificity in Non-Ribosomal Peptide Synthesis, on Tuesday, 9th July, 1 - 2pm in 4WW322 seminar room. All welcome!
Non-ribosomal peptides (NRPs) display a wide range of bioactivities, and comprise antibiotic, immunosuppressant, and cytostatic compounds. As such they represent an important source of essential medicines. NRPs are produced by ATP-dependent assembly line proteins known as non-ribosomal peptide synthetases (NRPSs). The therapeutic value of NRPs, and the modular nature of the assembly line, makes NRPSs attractive targets for reprogramming using synthetic biology. Despite recent successes, the design of synthetic NRPSs is hampered by limited understanding of their structure-function relationships, manifesting in low yields and a lack of diversity among synthetic products. On the contrary, evolution has repeatedly produced efficient NRPSs capable of producing diverse and structurally complex products. Currently, our understanding of how NRPS assembly lines evolve is rudimentary, and direct evidence supporting evolutionary hypotheses is rare. We have discovered a biosynthetic gene cluster in a Streptomyces sp. which encodes an NRPS capable of producing two related families of antibacterial hexapeptides. The organisation of the gene cluster, coupled with our biochemical analysis of the specificity conferring adenylation-domains, indicates a unique bifurcated mode of biosynthesis. Genomic analysis supports the emergence of the gene cluster through a combination of gene duplication and intragenomic recombination.
Thomas Booth graduated from the University of Manchester with first-class honours in biochemistry in 2014, during which time spent a year studying the evolution and biogeography of Pandanaceae at the Jodrell laboratory, Kew. Combining these interests, he recently completed his PhD in the lab of Barrie Wilkinson at the John Innes Centre, UK where he studied the evolution of metabolic diversity in Streptomyces natural products. He has also worked briefly outside of academia for the UK Government Office for Science. Thom currently works in the lab of Dr Yit Heng Chooi at the University of Western Australia, working to apply concepts of genome mining to a large scale dataset of Australian actinobacteria.
Weekly seminar schedule can be found here.