Mutasynthesis of Aureonitrile: An Aureothin Derivative with Significantly Improved Cytostatic Effect

Tapping nature's biosynthetic potential: Formation of the rare p-nitro benzoate precursor of aureothin, a mixed polyketide metabolite of Streptomyces thioluteus, requires two key enzymes: a p-amino benzoate synthase and an N-oxygenase. Feeding of surrogates to engineered block mutants (e.g. S. lividans ZX1::pHJ97) reveals that the iterative modular aureothin polyketide also accepts p-cyano benzoate as the starter, which is subsequently processed to the nitrile analogue of aureothin, aureonitrile, which has improved cytostatic properties.