Harnessing microbiota interactions to produce bioactive metabolites: communication signals and receptor proteins.

Numerous microbial communities live in soil, aquatic habitats, plants, and animal bodies. Microbial genome sequences have revealed that thousands of biosynthetic gene clusters (BGCs) are present in different bacteria and filamentous fungi. Many of these BGCs are not expressed in pure cultures in the laboratory. However, a large part of these silent clusters is expressed in nature when complex microbial populations are studied. The encoding specialized metabolites are frequently produced at very low concentrations but still they serve as communication signals that produce important biochemical and differentiation effects on other microorganisms of the consortium. Many specialized metabolites acting as communication signals have been identified, including autoinducers, intergeneric, and interkingdom cues. These signals trigger expression of silent BGCs in other microorganisms, thus providing new compounds with interesting biological and pharmacological activities. Examples of interactions between different bacteria or between bacteria and fungi are described here. Finally, the relevance of the human microbiota and the production in vivo of specialized metabolites of medical interest is discussed.