Naturally-occurring small molecules, especially bacterial secondary metabolites, have inspired researchers and physicians alike with their high degree of structural diversity and therapeutic potential. Among the many sources explored, microbial interspecies interactions have proven to be a rich source of novel secondary metabolites. My research has focused on a wide-spread symbiosis between a marine bacterium, Phaeobacter inhibens, and a microscopic alga, Emiliania huxleyi. Our lab recent proposed a biphasic symbiosis model for this algal-bacterial interaction, in which each phase is characterized by a set of small molecules (Figure 1). In the mutualistic phase, the algae provide a suitable surface for bacterial colonization, and the osmolyte dimethylsulfoniopropionate (1), serving as a source of carbon and sulfur for the bacteria. In return, the bacteria produce phenylacetic acid (2), a growth promoter for the algae, and the antibiotic, tropodithietic acid (TDA, 3), which protects the algal host against pathogenic bacteria. When the algae senesce, however, the interaction switches to a parasitic mode. The switch is triggered by the release of a lignin breakdown product, such as p-coumaric acid (4), by an aging algal host. In response, the bacteria produce a family of potent algaecides, roseobacticides (5), which kills the algae with nanomolar to micromolar efficiency. The two structurally unusual troponoids, TDA and roseobacticide, play an important role in defining this dynamic symbiosis, and highlight the structurally and functionally versatile secondary metabolites bacteria can make in response to different signals. In addition, roseobacticides constitute a new structural class of natural products, suggesting that new enzymatic transformations govern their production. However, little is known about the biosyntheses or mode of action of roseobacticides and TDA. In this talk, I will present the insights we've recently gained into this symbiosis by 1) investigating roseobacticide and TDA biosyntheses, and 2) studying the mode of action of the broad-spectrum antibiotic, TDA.

Investigating the molecular basis of algal-bacterial symbioses

253rd National Meeting (2017)

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