The first part of the invention is a sophisticated tool that screens for gene clusters encoding bioactive compounds. Only clusters that can be expressed in the bacterium E. coli will be recovered, ensuring that the bioactive polyketide and unusual peptide molecules that they encode can be produced cheaply through fermentation, and in unlimited supply. This is a new tool to aid drug discovery from natural sources, examples of environments that can be accessed are the mixed bacterial communities in soils, marine sediments, or marine sponges. A manuscript describing a proof-of-principle application of the invention has just been accepted by the A* ranked journal Environmental Microbiology (Owen JG, KJ Robins, NS Parachin and DF Ackerley. 2012. A novel functional screen for recovery of 4’-phosphopantetheinyl transferase and associated natural product biosynthesis genes from metagenome libraries. Environmental Microbiology In Press.) The second part of the invention is an entirely new, rapid, inexpensive and versatile approach to take aim at a previously inaccessible drug target present in many bacteria. The target is a PPTase enzyme (full name: 4’-phosphopantetheinyl transferase enzyme), which pathogenic bacteria such as Pseudomonas aeruginosa and Mycobacterium tuberculosis require for fatty acid synthesis, as well as making a number of virulence factors and secondary metabolites. Our screening technology can readily be applied to identify novel antibiotic compounds in large chemical collections, with simple counter screens available to ensure antibacterial activity and high therapeutic index.
Seeking industrial partners who are interested in either licensing this technology, or collaborative research towards commercial outcomes.
Proof of Concept - Early prototype built