Lay summary
The goal of this Hercus Fellowship is to develop approaches for engineering the biosynthesis of non-ribosomal peptides with improved anticancer activity. Microbes produce these small peptides using modular enzymes in which each module adds one amino acid to the final peptide product. While evolution has driven an enormous diversity of bioactive natural products, it is apparent from the disadvantages of current drugs that nature does not present an already optimised product. This is unsurprising given the microbes producing these compounds have been under no evolutionary pressure to treat human conditions. As their complex structures often impedes synthesis, improved lead molecules have generally emerged from relatively small numbers of synthetic analogues. In contrast, biosynthesis of these compounds is performed in a modular assembly-line like manner, which suggests that synthetic biology could be used to overcome this problem by substituting modular units at a genetic level to explore new chemical diversity.