Sir James Black Prize Lecture
Engineering metabolic pathways in microorganisms can provide new antibiotics and other bioactive natural products. The mupirocins, e.g., pseudomonic acid A and thiomarinols isolated from Pseudomonas and Pseudoalteromonas bacteria, are antibiotics active against MRSA. Clinical applications are restricted by instability in the former and toxicity in the latter. Using classical biosynthetic methods to understand how they are formed, combined with molecular genetic engineering, novel analogues in which both these limitations can be produced. Similarly, the biosynthetic pathway to the fungal metabolite, tenellin, isolated from Beauvaria bassiana, has been engineered to produce the ‘extinct’ compound, bassianin, and many new compounds for biological evaluation.
Professor Thomas Simpson FRS FRSE, Alfred Capper Pass Professor of Chemistry, University of Bristol