Molecules Made by Cyanobacteria Are Scattered Among Different Species

A particular species of marine cyanobacteria holds less potential for medicinal use than originally thought, according to an international study led by researchers at the Scripps Institution of Oceanography at UCSD.

“Marine cyanobacteria of the genus Lyngbya are among the richest sources of bioactive natural products. We need to learn as much as possible about these fascinating organisms in our search for new drug candidates,” Scripps graduate student and first author of the paper Adam Jones said.

The recent rise in marine biomedicine first prompted the researchers to conduct this study. The FDA is increasingly approving drugs derived from ocean life, such as the pain reliever Prialt and anticancer agent Halaven. L. majuscula, the tropical microorganism of interest in this study, was previously known to produce molecules that could treat cancer, malaria and inflammatory diseases.

Despite their biomedical promises, however, little is actually known about the genetics that give rise to the production of potential drugs derived from organisms of the Lyngbya genus, including L. majuscula.

Jones and postdoctoral fellow Emily Monroe of the Gerwick Laboratory at Scripps finally cracked the genetic code of L. majuscula, completing a project that began back in 2005. The genome was published on May 9 in the Proceedings of the National Academy of Sciences.

This study marks the first time that the genome of a filamentous marine cyanobacterium has ever been sequenced.

A major obstacle to sequencing these cyanobacteria has been contamination by other bacterial strains. Because other bacteria cling to the outer sheath of L. majuscula and contaminate these samples, the researchers had to use both traditional and modified methods for DNA isolation.

In the modified approach, single cells were isolated under the guidance of a microscope. The small amounts of DNA were then amplified using a technique called Multiple Displacement Amplification, and bioinformatics tools were used to eliminate the background noise of any contaminating bacterial sequences.

The results revealed an intricate network of genes that enable L. majuscula to interact with other bacteria and adapt to environmental conditions. In contrast to previous reports, the study also found that this strain cannot use atmospheric nitrogen in a process known as nitrogen fixation, which is necessary to synthesize the building blocks of life.

To the researchers’ surprise, the marine organism only had eight sets of genes dedicated to the biosynthesis of molecules that could be potential drug candidates.

“Three of these were involved in making the molecules we had found earlier,” Jones said. “The other five sets likely are responsible for making new molecules we’ve never seen, but follow-up experiments revealed that these genes did not appear to be active in our culture conditions.”

Still, according to the paper, 35 percent of all natural products from cyanobacteria come from the Lyngbya genus alone. Jones foresees using the successful isolation techniques from this study to sequence the genomes of related species and identify which species of the Lyngbya genus are actually responsible for producing molecules useful for human drug development.

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