Seminar: Observation and exploitation of megasynth(et)ase evolution
Polyketides and nonribosomal peptides are important classes of natural product used in the pharmaceutical and agrichemical industries with antibacterial, antifungal and anticancer properties. Diversification of these modular megasynth(et)ase enzymes can occur through duplication, deletion or recombination events within their biosynthetic gene clusters.
Using a unique collection of 200+ genome sequenced Burkholderia gladioli strains, we directly observe evolution in action through intra species genomic analyses. We uncover multiple examples of polyketide synthase and nonribosomal peptide synthetase variants formed through recombination events and detect the associated natural product derivatives. These recombination principles were subsequently applied to Pseudomonas lipopeptide NRPS systems to generate novel derivatives alongside unexpected recombination events. The use of evolution-based non-specific splice sites offers an exciting approach to rational and reliable megasynth(et)ase engineering.
Speaker
Dr. Alex Mullins undertook a PhD and postdoctoral position at Cardiff University focused on Burkholderia biopesticides and their safety, efficacy, and persistence in the environment. This work combined genomics, molecular microbiology, specialised metabolite characterisation, and plant-based biocontrol experiments. Following a brief fixed-term lectureship in bioinformatics, Alex started a BBSRC Discovery Fellowship at the University of Warwick investigating megasynth(et)ase evolution and evolution-inspired engineering of megasynth(et)ases.