Engineering enzymatic assembly lines for the production of new antimicrobials

A large portion of natural products are biosynthesized by the polyketide synthase and non-ribosomal peptide synthetase enzymatic assembly lines. Recent advancements in the study of these megasynthases has led to many new examples that demonstrate the production of non-natural natural products. The field is likely nearing the ability to design and build new biosynthetic pathways de novo. We discuss the various recent approaches taken towards this goal, focusing on the installation of new substrates, the swapping of enzymatic domains and modules, and the impact of metabolic engineering and synthetic biology. We also address the challenges remaining alongside the many successes in this area.