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Business Growth
Dec 1, 2015

‘Genome Mining’ Teases Secrets Out Of Natural Substances

Sponsored Content provided by Daniel G. Baden - Executive Principal, Marine Biotechnology in North Carolina (MARBIONC)

A research center devoted to marine biology, like UNC Wilmington’s MARBIONC Center, is based on the idea of close collaboration among scientific disciplines. In one important current project, biologists are studying marine organisms to identify new chemical compounds and collaborating with chemists who work with those compounds on the molecular level.
Those specialists pass their findings on to medical researchers, who test these new compounds as possible new drugs.
Clinical research, to see the effect of a new substance on animals or humans, attracts plenty of attention. But before that can happen, a lot of painstaking basic science has to be done, largely behind the scenes. Researchers are puzzling out the relationships between living cells, their genetic material, and the complex molecules they produce. Understanding those relationships makes it possible to create entirely new substances, and to find new ways to produce them in the quantities needed to develop new medical therapies.
A team of chemists based at UNCW’s CREST Research Park is doing what we call “genome mining.” Their objective is to understand the underlying chemistry by which microscopic algae produce potentially useful and “biologically active” compounds. Jeffrey Wright, Ph.D., and Wendy Strangman, Ph.D., are two of the faculty scientists leading this project.
So far, in studying blue-green algae found in seawater as well as similar freshwater species, Strangman reports, we have isolated and purified more than 160 new compounds. Not surprisingly, considering that one of the sources is the dinoflagellate that produces the notorious fish-killing “red tide,” a third of these compounds are toxins. Others show signs of being biologically active in more benign and possibly beneficial ways, she explained.
Analyzing the DNA that allows an organism to create one particular molecule often shows us the potential to create other similar compounds that might have very different effects or uses. We refer to those groups of substances that the cell’s DNA could – or should – be making as “cryptic biosynthetic clusters.” That is one way that we can adapt what humble algae produce to help us create entirely new compounds.
Another way is by analyzing the intricate three-dimensional structure of molecules called “stereocenters,” many of which are among the materials we have extracted from marine algae. Rearranging the component parts of these complex molecules – putting the same pieces in different positions – creates new substances that often have very different effects.
The result is what we call “semisynthetic compounds.” They may not be found in nature, as far as we know, but they are close cousins to chemicals we have discovered in our marine algae cultures. A microbe made the original molecule. We use the tools of chemistry to modify the molecule, hence the “synthetic.” The “semi” means we can’t take full credit for developing something that originated in nature.
Analyzing a microbe’s genome can help us figure out ways that tinkering with nature’s recipe, maybe by adding more of certain enzymes, might help speed up production of a particular biological compound. That can have obvious benefits if the substance proves to be useful. Many of the compounds we have discovered exist in tiny amounts. Before they can be thoroughly studied we have to figure out ways of making much larger quantities.
Our collaborators who are doing actual biomedical research, working with live creatures – we mostly test these substances on cell cultures in petri dishes – work in synergy with our researchers. When we discover biological activity, meaning a compound has an effect on a cell, we typically do two things. We pass on our findings to those who will take the next step in research. We also work to scale up production of that promising chemical so enough is available to do meaningful experiments.
UNCW CREST Research Park is a frontrunner in marine biotech research and development. Researchers are exploring the potential of natural products derived from the sea to treat or cure human diseases and meet other important needs.
Discover why rising biotechnology and life sciences groups from all over the country are moving to UNCW CREST Research Park. UNCW CREST Research Park offers top-notch commercial laboratories available for lease at affordable rates, flexible terms, and innovative product development opportunities that are unmatched by any other park. Connect with CREST at [email protected] today.

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