The benefits of living together – studying marine symbioses to discover enzymes for biotechnology applications

Over the past 50 years, more than 15 pharmaceuticals derived from marine organisms have come to the market. Most of these come from filter-feeding invertebrates that contain a high proportion of microbial symbionts. Microbiology and molecular genetic studies have shown that many of these drug-like compounds are produced by the microbial symbiont. The enzymes that produce these compounds are promiscuous meaning they can process a diverse range of related substrates, making them extremely attractive to the biotechnology industry. Determining the structure of these enzymes makes them amenable to engineering, allowing them to process non-natural substrates. Using this approach, synthetic substrates can be treated with a cocktail of enzymes to prepare focused libraries of compounds to hit drug targets such as protein–protein interactions. These targets are involved in a range of diseases from cancer to immune disorders and are hard to modulate using small molecule drugs. Complex modified cyclic peptides produced using a chemoenzymatic process may be a promising approach to address these disease conditions.