Coauthors of the paper include (from left) William Gerwick, Emily Monroe, Adam Jones, Lena Gerwick, Sheila Podell, and Eduardo Esquenazi. Photo: UC San Diego |
An
international team of researchers led by scientists at Scripps Institution of
Oceanography at UC San Diego has deciphered the genome of a tropical marine
organism known to produce substances potentially useful against human diseases.
Tiny
photosynthetic microorganisms called cyanobacteria are some of the oldest forms
of life on the planet. At times their emergence as toxic blooms causes a threat
to humans and animals. But despite the recognized capability of marine strains
of the cyanobacterial genus Lyngbya, and specifically the species L.majuscula, to create hundreds of natural products with biomedical
promise, surprisingly little is known about the genetics underlying their
production.
In an
online early edition of the Proceedings of the National Academy of Sciences,
a research team led by Scripps graduate student Adam Jones and postdoctoral
fellow Emily Monroe, both in the Gerwick laboratory at Scripps Institution of
Oceanography’s Center for Marine Biotechnology and Biomedicine (CMBB), provide
the first insights of the genome of Lyngbya majuscula 3L, a Caribbean
organism that generates compounds that are being developed for potential
treatment against cancer and neurodegenerative diseases.
“These
compounds have gained considerable attention due to their pharmaceutical and
biotechnology potential, but they are also notorious for their environmental
toxicity and threats to humans, wildlife, and livestock,” the authors note in
their paper.
In the
marine environment the wiry, or “filamentous,” cyanobacteria play a vital role
in the global carbon cycle. Lyngbya strains are known to disrupt the
healthy growth of coral reefs and are behind the agents responsible for a skin
rash known as “swimmer’s itch.”
Achieving
the first genomic sequencing of its kind for the filamentous Lyngbya
majuscula 3L, the research team overcame several obstacles due to the
organism’s complex, intermeshed growth in the wild with a range of other
bacteria, muddying a clear picture of the genome. The team undertook several
different research tactics and experiments, including single cell genome
amplification, protein and metabolite profiling.
The
results revealed a complex gene network suggesting an enhanced ability of the
organism to adapt to shifting conditions in the marine environment.
Adam Jones collects samples in Papua New Guinea. Photo: UC San Diego |
Sequencing
was done at the Max Planck Institute in Berlin, Germany and at the J.Craig Venter Institute in Rockville, Maryland.
Much of the assembly was conducted by Sheila Podell, a project scientist in the
Eric Allen laboratory at Scripps. Jones and Monroe traced the genomic pathways
and performed tests to understand which genes encoded the production of
different natural products.
Yet as
much as the genome revealed about Lyngbya majuscula 3L, the
researchers also uncovered key information about its limitations and
shortcomings. For example, it’s been assumed that Lyngbya majuscula 3L
and its cousins in the Lyngbya genus convert, or “fix,” nitrogen from the
atmosphere into organic molecules, a fundamental natural process in the global
environment. To their surprise, Lyngbya majuscula 3L lacks the genes
necessary for nitrogen fixation, even though reports exist that this species
fixes nitrogen.
“It’s
possible that strains of L. majuscula reported to fix nitrogen may
have been misidentified because it is visually very similar to other
filamentous cyanobacteria species and we found that this marine strain doesn’t
seem capable of fixing nitrogen on its own,” said Monroe. “This feature could
be a distinction between the freshwater and the marine strains of what is
currently characterized as Lyngbya.”
And while
marine Lyngbya strains are proven prolific generators of natural
products with biomedical and pharmaceutical potential, the new study shows that
more work is needed to pinpoint which species generates which natural products.
Jones says that more than 250 compounds are attributed to marine Lyngbya
strains. Of those, nearly three-quarters are linked to Lyngbya
majuscula. However, the Lyngbya majuscula 3L strain was found to
only produce a small number of natural products.
“This
particular strain doesn’t produce nearly as many (natural products) as we
thought it might, which shows that many of the interesting molecules discovered
to date are probably scattered among multiple organisms,” said Jones. “The
lesson learned is that not all marine Lyngbya strains are created
equal.”
“This may change the way we start looking at things
in the field and give us new ways to identify organisms,” said Lena Gerwick,
the faculty member who organized this genomic project from the beginning. “We
might be able to turn things around and use the compounds they make as a new
way of determining what kinds of species they are.”
