Enormous enzymes expand the limits of molecular biology

For natural-product chemists, polyketides offer a high-stakes game. These typically polycyclic fused-ring carbon molecules are made by bacteria, algae, plants, fungi and some animals for a variety of purposes. Many polyketides are highly toxic, and they are key culprits in the devastating ecological effects of algal blooms that have episodically decimated local fish populations around the world. That toxicity, however, is partly what makes some polyketides candidate anticancer agents, which in turn makes them attractive targets for total synthesis. But one look at the complex structures, with their plethora of chiral centres, and the magnitude of that task is clear.