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Phaeobacticides - Potent and selective new class of algae growth inhibitors

Algae are a diverse group of uni- and multicellular plants that grow in water. Undesired and uncontrolled algal blooms are a recurring problem in bodies of water such as swimming pools, aquaculture ponds, aquariums, industrial drainage systems and even the ocean. Various strategies have been used to control algal growth – previous attempts to solve the problem included the use of active chlorine, copper-containing compounds or quaternary ammonium salts. Most of these approaches have severe drawbacks, and chemicals that are commonly used can be toxic, corrosive, decompose readily and precipitate in hard water. Hence, the need for safer algicides remains.

Algal-bacterial symbiosis: Eukaryotes, including algae, evolved on the planet teeming with bacteria and close associations between eukaryotes and bacteria are common. Microscopic algae, in particular, co-exist symbiotically with bacteria of the roseobacter clade. Bacterial metabolites can serve as antibiotics and auxins, which suppress the growth of potentially parasitic bacteria and promote algal growth, respectively. The algae, in turn, contribute a suitable surface for roseobacter to colonize. In some cases, as the algae die, the bacteria switch from being a mutualist to a pathogen.

Phaeobacticides – a new class of potent phytotoxins: Researchers in the Clardy and Kolter laboratories have discovered that a small molecule generated by compromised algae induces the roseobacter species to produce potent but selective phytotoxins. The researchers hypothesized that the initiator of the mutualist-to-pathogen switch would be produced by compromised algae – as algae senesce, their cell walls deteriorate and breakdown products are released into the surrounding medium. They therefore used a breakdown product of a component of the cell wall as a tool to study the response of three roseobacter strains to a compromised algal host. Culturing one specific strain with this breakdown product stimulated the production of a family of compounds that were not produced in the absence of the breakdown product. Two of these compounds, phaeobacticides A and B, were purified and further characterized:

• Phaeobacticides form a new class of compounds: Researchers used a combination of analytical techniques – mass-spectrometry, x-ray crystallography and magnetic resonance to elucidate the small molecule structures of these compounds. Compounds A and B are structurally similar, and have no close relatives among known natural products or synthetic molecules. Very recent work has expanded the family of known molecules to over a dozen.

• Phaeobacticides are potent phytotoxins: Algicidic activity of the two small molecules was measured against a panel of algae species. In several cases, the compounds were highly active – for example, the IC50 of phaeobacticides A and B against two common algae species was in the 0.1-0.2 µM range. In many cases algal cell lysis was observed after 24 hrs with cellular damage visible after 12 hrs.

• The small molecules are selective: No antibacterial activity was observed at concentrations up to 0.16 mM and some algae species were less susceptible to the compounds. Taken together, the facts suggest that phaeobacticides are not generally toxic and can selectively impair particular species, an important advantage over some of the currently used chemicals.

Intellectual Property Status: Patent(s) Pending

Applications

The invention addresses the need for a low-toxicity anti-algae agent that can be used in a variety of settings:

• Preventing algal growth in bodies of water: Algal blooms, if left unchecked can multiply to the point of rendering the water unfit for human use. The “pond moss”, greenish mats on the water surface can serve as the source of toxins, as well as physically block fish gills, fishing nets and water supply systems. As outlined above, most of the currently used algicides are non-specific chemicals, while phaeobacticides are the unique example of a natural product optimized to specifically target algae cells. The approach used by researchers in Clardy and Kolter laboratories can be extended to other bacterial strains and algae species resulting in a panel of phaeobacticides with different specificities. Also, phaeobacticides can be used in a combination with fungicides and bactericides. Such combinations might be less toxic and more efficient towards resistant pathogens.

• Algae-resistant materials: Being stable small molecules, phaeobacticides can be easily incorporated into a variety of materials or industrial products which are in prolonged contact with water. Few examples include fishing nets, swimming pool plastic coating, exterior paints, and synthetic resin renderings for heat protection.

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