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| Seabed in the Royal National Park, New South Wales--Courtesy of Toby Hudson/CC BY-SA 3.0 |
A new genetic platform that enables scientists to synthetically produce naturally occurring molecules could help propel new drug development by opening up access to marine microbiota that's previously proved difficult to harness.
"What we're seeing is that it's becoming more difficult to find new chemicals from nature to put in our drug-discovery pipeline," Bradley Moore, a professor of oceanography and pharmaceutical sciences at the University of California, San Diego, told FierceBiotechResearch. "So we've taken a different approach. We are sequencing marine genomes and looking for the genetic potential for these molecules to have drug properties."
The approach, developed by Moore and his team, allows for the efficient production of naturally occurring molecules and is based on a technique called transformation-associated recombination (TAR) cloning. Using TAR cloning, the researchers produced a synthetic version of Saccharomyces cerevisiae, a species of yeast. The researchers looked for sequences of interest in the yeast genome using next-generation sequencing technology. They then targeted a specific area on the genome--the taromycin gene cluster--that would encode an antibiotic molecule from ocean bacteria. The taromycin gene cluster bears a close resemblance to the biosynthesis pathway of daptomycin, a clinically approved antibiotic used to treat infections caused by multidrug-resistant bacteria. This "plug-and-play" approach produced a new antibiotic in the lab, dubbed taromycin A.
The research is published in the Proceedings of the National Academy of Sciences.
Microbes are able to biosynthesize a wide range of specialized compounds. Next-generation sequencing technologies make it possible to screen such compounds for drug potential, but scientists still don't have an efficient way to link genes with specific molecules. A major challenge with synthesizing ocean microbiota has been the inability to grow and maintain these ecosystems in a lab setting.
"Marine bacteria are a source of organisms that has not been developed in full as a lot of terrestrial microbes have in the past decades," Moore said. "With that genetic and biological diversity comes greater diversity in genome sequences. We'd like to use this tech to better tap that chemical diversity and apply it to drug screens."
- here's the study abstract
- read the press release
Editor's Corner: Biosortia tapping into nature to fill early drug-discovery void