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Synthetic Bio Platform Finds Potential Superbug Antibiotic

Saccharomonospora bacteria

Scanning electron micrograph of Saccharomonospora bacteria (National Library of Medicine)

Researchers at University of California in San Diego created a process for cloning synthetic gene clusters from marine bacteria that generate molecules with therapeutic potential, and produced an antibiotic candidate to treat previously drug-resistant infections. The team led by UC-San Diego oceanography and pharmacy professor Bradley Moore, published its findings yesterday online in the journal Proceedings of the National Academy of Sciences (paid subscription required).

The university’s technology transfer office applied for patents on both the cloning process and the antibiotic generated by that process, with each disclosure listing Moore as the inventor.

The research team — with colleagues from UC-San Diego, JNC Corporation in Japan, and University of British Columbia in Canada — sought a method for capturing more of the specialized compounds that microorganisms can produce, but under lab conditions are often difficult to create. The problem is particularly acute, say the researchers, with ocean microorganisms that are difficult to grow or express all of their capabilities in the lab.

Moore and colleagues used a technique known as transformation-associated recombination that can isolate clusters of genes from complex genomes. The researchers adapted recombined gene clusters from yeast, by working with high-throughput sequencing to clone gene clusters from the marine Saccharomonospora bacteria.

These synthesized gene clusters express a lipopeptide — a combination of lipid and peptide — with antibiotic properties the researchers call taromycin A. This antibiotic is chemically similar to the FDA-approved antibiotic daptomycin, marketed as Cubicin by Cubist Pharmaceuticals, a treatment for complicated Staphylococcus aureus infections including those from methicillin-resistant or MRSA bacteria.

The researchers believe the technology can open-up previously difficult to access biological pathways to generate new drug candidates. Moore says in a university statement, “the new synthetic biology technology we developed – which resulted in the discovery of a new antibiotic from a marine bacterium – is just the tip of the iceberg in terms of our ability to modernize the natural product drug discovery platform.”

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