A volcano-loving bug offers clues as to what makes life possible in extreme conditions.

by Dr David Noever

They may be small, but they're very hot. They're the archaea, an ancient branch of microbial life on Earth discovered by scientists in 1977. Unlike the better known bacteria and eukaryotes (plants and animals), many of the archaea can thrive in extreme environments like volcanic vents and acidic hot springs. They can live without sunlight or organic carbon as food, and instead survive on sulfur, hydrogen, and other materials that normal organisms can't metabolize. It may sound like science fiction, but many scientists are working rapidly to explore the biology as well as the practical benefits of these life forms.

An enzyme, alcohol dehydrogenase (ADH), is derived from a member of the archaea called Sulfolobus solfataricus. It works under some of nature's harshest volcanic conditions: It can survive to 88 deg. C (190 deg. F) - nearly boiling - and corrosive acid conditions (pH=3.5) approaching the sulfuric acid found in a car battery (pH=2). ADH catalyzes the conversion of alcohols and has considerable potential for biotechnology applications due to its stability under these extreme conditions. To understand how it works, scientists first need to learn its basic structure. For this, an Italian research team went to space.

After collecting Sulfolobus solfataricus from the Solfatara volcanic area near Naples, the Italian team used the ADH enzyme for crystallization aboard the Space Shuttle.

Compared to crystals grown in Earth's gravity, the space crystals showed an improved quality of nearly 35%, and the researchers obtained diffraction data with a significantly higher resolution, indicating reduced disorder. Scientists hope to use the space grown crystals to improve the biological understanding of how these molecules work based on a detailed knowledge of their shape and exact atomic positions.

A fundamental question posed by the space shuttle investigation is: what features of these volcanic microbes' metabolism allows for such thermal stability in their enzymes? If unusual characteristics in their metabolism can be identified and studied, the transfer of this knowledge is almost immediate to applications in environmental cleanup, pollution prevention, or energy production. Many researchers envision a range of medically, industrially, and environmentally useful compounds derived from the extreme heat-loving, or "hyperthermophilic" Archaea.

Biomolecules from these organisms are active at temperatures that generally degrade normal cellular molecules, such as enzymes, lipids, and nucleic acids.

When stored at room temperature, these molecules from volcanic microbes are in the "deep freeze" compared to their normal lives, thus offering tremendously extended shelf-life and stability in commercial use.

The first Archaea-related products were DNA polymerases for the research market. For example, New England Biolabs, a Beverly, Mass.-based biotechnology company, sells Vent and Deep Vent polymerases, used in DNA sequencing. These enzymes originally were isolated from hyperthermophiles associated with oceanic hydrothermal vents. Without analysis of these fiery microbes, neither the modern identification of human genetic diseases nor the use of DNA evidence in legal courts would even have been realized.

Researchers say that the heat and geochemical conditions in volcanic regions may be similar to conditions that existed on the young, water-covered, cooling Earth. Almost like a creature from science fiction, the volcanic microbe is different from the two other basic branches of life: bacteria and eukaryotes. The prokaryotes are the bacteria, while eukaryotes are the so-called higher forms of life, including humans, plants and animals.

A major difference is that eukaryotes put their genes inside a nucleus, while prokaryotes do not. In the archaea, there is no nucleus, but many genes behave like those in higher organisms. Archaea are thought to have a common ancestor with bacteria, but billions of years ago the third domain, eukaryotes, broke off from archaea, eventually developing into plants, animals and us. Archaea include microbes that live at the extremes of the planet - the very, very cold, hot or high-pressure places that no other form of life could endure.

As such, archaea are the extremophiles who boldly thrive where no other life form would go. Some scientists have suggested that as such, archaea may represent the earliest form of life and thus may be the most likely form of life existing on other planets. About 500 species of archaea are now identified, but speculation may not be far off in projecting that given the difficulties of collecting and classifying them, there may be a million others. The life form is thought to produce about 30 percent of the biomass on Earth, much of it in the Antarctic Ocean.

In fact, as far back as 1994, Myrna Watanabe, a biotechnology consultant, wrote that the existence of this third branch of life "here on Earth has led scientists to realize that planets they hitherto assumed to be lifeless might support life."

Some estimates suggest that human biology depends on the action of nearly half a million different enzymes and proteins. In fewer than 1 case in 100, we have a three-dimensional picture of shape and function of these complex chemicals. Since 1984, the Space Shuttle has carried experiments to determine the structures of large, biologically important molecules. This research has compiled results for a host of human diseases ranging from insulin (for the control of diabetes) to one enzyme called reverse transcriptase that can be blocked to inhibit HIV infection.

In comparing more than 33 such different biological molecules crystallized on the Shuttle and also in similar conditions on earth, space produced larger space crystals in 45% of the cases and new structures in nearly 20% of the cases. As many as half the space crystals had a 10% or better improvement in the x-ray brightness or the crystallographic resolution. Both are important to determining these large molecules' shape and exact atomic positions.

Much work remains to be done in uncovering the shape and detailed way that these extreme microbial molecules achieve their thermal stability. In a controlled study comparing space grown crystals with the best data ever previously obtained from ADH crystals formed on Earth, the Italian team found that the "the microgravity-grown crystals displayed increased stability when exposed to X-rays." This finding moves the investigation closer to revealing the biological function of these complex molecules.

According to their report, although future flights will be required to solve the fully three-dimensional picture of the molecule, the Space Shuttle provided larger, more ordered and more radiation-stable examples of this microbial enzyme; and as our knowledge grows we are being offered increasing and important insights as to what makes life possible in extreme conditions.