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Regulation of biosynthesis - Professor George Salmond

Abstract:

Food security, biotechnology, quorum sensing and flotation: antibiotics from biocontrol bacteria and plant pathogens active against other plant pathogens!    We work on bioactive molecules called heterumalides. They have potent anti-oomycete activities (e.g. against Phytophthora, the potato blight pathogen) and antifungal properties. They also have anti-cancer activities. Some Gram-negative bacteria make bioactive haterumalides such as oocydin A (which is a potent anti-oomycete). We defined large gene clusters in environmental isolates of the enterobacterium, Serratia, responsible for oocydin biosynthesis and we have studied the production of the molecule using mutants (both by transposon mutagenesis and through allelic engineering), bioassays, and chemical analysis (with Dr Leeper in the Chemistry Department). Various plant pathogens can make the molecule, or analogues. We have used bioinformatics, physiological studies and gene fusion techniques to investigate regulation of biosynthesis in Serratia. This project will involve a molecular biological study of bacteria that make the bioactive molecule(s), investigating environmental and physiological signals (including Quorum Sensing) that act as regulatory inputs to production of oocydin and other bioactives. Given the impact on phytopathogens, this project has obvious “food security” importance, but is also pertinent to the “industrial biotechnology” theme because of possible translational utility, and “synthetic biology” because of the opportunities for engineering genes and gene clusters for production of new, bioactives, including in bacterial pathogens that are capable of flotation!

References:

  1. Matilla, MA et al (2012) Bacterial gene clusters encoding the anti-cancer haterumalide class of molecules: biogenesis of the broad spectrum antifungal and anti-oomycete compound, oocydin A. Journal of Biological Chemistry, 287: 39125-39138
  2. Ramsay, J., et al (2011) A quorum-sensing molecule acts as a morphogen controlling gas vesicle organelle biogenesis and adaptive flotation in an enterobacterium. PNAS, USA 108, 14932-14937
  3. Poulter, S., et al (2011) The Serratia LuxR-family quorum sensing regulator, CarR, activates transcription in the absence of N-acyl homoserine lactone signals. Molecular Microbiology, doi: 10.1111/j.1365-2958.2011.07634.x

Professor George Salmond

Professor George Salmond
Department of Biochemistry
Office Phone: 01223 333650