Volume 2, Issue 17 December 2005/January 2006
Extreme Biomaterials
A fellow of the American Association for the Advancement of Science (AAAS), Douglas Clark is also a scientist with the Lawrence Berkeley National Laboratory's Environmental Energy Technologies Division.
In the deepest oceans, near incredibly hot volcanic vents, a strange, hearty organism survives and thrives. Many scientists study these microorganisms, called extremophiles, for the clues they may hold about the origins of life. UC Berkeley chemical engineer Douglas S. Clark is interested in them for a different reason. The extremophiles contain enzymes that spur biochemical reactions even in the harshest conditions. And much of Clark's research is concerned with novel enzymatic reactions, particularly how they may improve industrial processes and aid in pharmaceutical production.
First identified in the 1970s, extremophiles live in conditions that are either far too hot, cold, acidic, alkaline, or salty for most other organisms. They've been found happily swimming through sewage, petroleum deposits, hot springs, and other seemingly-inhospitable locales. To analyze the extremophiles that call the deep sea thermal vents home, Clark and his colleagues have constructed a laboratory apparatus that mimics the extremophile's natural home. By studying the extremophiles under their preferred conditions, the researchers can begin to identify the genes, proteins, and biological processes that keep the bizarre creatures alive under extreme conditions.
Scanning electron micrograph of cells of Methanocaldococcus jannaschii, a methane-producing extremophile isolated from the vicinity of a deep-sea hydrothermal vent. (courtesy the researchers)
"That knowledge might enable us to genetically engineer more conventional organisms to tolerate a wider range of conditions in industrial practice," Clark says.
Enzymes are used in myriad commercial products and processes, from detergents to DNA fingerprinting to food production. However, all enzymes are sensitive to their environment, requiring careful monitoring and control of temperature, pH levels, or other factors to keep them cranking away. So-called extremozymes that remain productive even in changing environments would be a boon to industry.
For example, many industrial processes require organic solvents to dissolve a substrate or compound in the course of a chemical transformation. While solvents sometimes deactivate enzymes, certain extremozymes could likely withstand such a brutal bath. In addition to characterizing these catalysts, Clark is exploring whether proteins borrowed from the extremozymes might be used to stabilize traditional enzymes in extreme industrial conditions.
The Clark Group has constructed specialized containers like this one that can duplicate the most extreme conditions on Earth known to support life. (courtesy the researchers)
The Clark group is also learning to hijack the extremophiles' cellular machinery for the production of natural compounds like pharmaceuticals. The biochemical pathways that the extremophiles use to form proteins could potentially be transferred to another organism that's "programmed" to produce a certain bio-therapeutic compound. The engineered organism--souped up with the extremophiles' robust protein-folding machinery--would become a much more efficient drug factory.
The researchers have also begun to examine the physiology of extremophiles as a direct source of useful bioproducts. Recently, they discovered a protein in a particular extremophile that forms long, stable filaments. Clark believes these tiny tendrils could possibly be used as nanowires in future integrated circuits or even to pattern other materials on very small scales, a key challenge in nanoengineering.
"Our focus is devising ways to improve the utility of biological systems for practical applications," says Clark, who previously developed a "biochip" for drug toxicity screening that mimics the human liver. "Extremophiles may be a source of new enzymes and proteins that could help us meet that objective."