Synthetic fermentation of bioactive molecules.

The concept of synthetic fermentation is to 'grow' complex organic molecules in a controlled and predictable manner by combining small molecule building blocks in water-without the need for reagents, enzymes, or organisms. This approach mimics the production of small mixtures of structurally related natural products by living organisms, particularly microbes, under conditions compatible with direct screening of the cultures for biological activity. This review discusses the development and implementation of this concept, its use for the discovery of protease inhibitors, its basis as a chemistry outreach program allowing non-specialists to make and discover new antibiotics, and highlights of related approaches.