Phylogenetic analysis of the salinipostin γ-butyrolactone gene cluster uncovers new potential for bacterial signalling-molecule diversity

Bacteria communicate by small-molecule chemicals that facilitate intra- and inter-species interactions. These extracellular signalling molecules mediate diverse processes including virulence, bioluminescence, biofilm formation, motility and specialized metabolism. The signalling molecules produced by members of the phylum Actinobacteria generally comprise γ-butyrolactones, γ-butenolides and furans. The best-known actinomycete γ-butyrolactone is A-factor, which triggers specialized metabolism and morphological differentiation in the genus Streptomyces . Salinipostins A–K are unique γ-butyrolactone molecules with rare phosphotriester moieties that were recently characterized from the marine actinomycete genus Salinispora . The production of these compounds has been linked to the nine-gene biosynthetic gene cluster (BGC) spt. Critical to salinipostin assembly is the γ-butyrolactone synthase encoded by spt9. Here, we report the surprising distribution of spt9 homologues across 12 bacterial phyla, the majority of which are not known to produce γ-butyrolactones. Further analyses uncovered a large group of spt-like gene clusters outside of the genus Salinispora , suggesting the production of new salinipostin-like diversity. These gene clusters show evidence of horizontal transfer and location-specific recombination among Salinispora strains. The results suggest that γ-butyrolactone production may be more widespread than previously recognized. The identification of new γ-butyrolactone BGCs is the first step towards understanding the regulatory roles of the encoded small molecules in Actinobacteria.