Published online 2 December 2010 | Nature | doi:10.1038/news.2010.645

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Oddball bacterium can survive without one of biology's essential building blocks.

A bacterium in California's arsenic-filled Mono Lake performs a novel chemical trade-off. Feargus Cooney/Lonely Planet Images

A bacterium found in the arsenic-filled waters of a Californian lake is poised to overturn scientists' understanding of the biochemistry of living organisms. The microbe seems to be able to replace phosphorus with arsenic in some of its basic cellular processes — suggesting the possibility of a biochemistry very different from the one we know, which could be used by organisms in past or present extreme environments on Earth, or even on other planets.

Scientists have long thought that all living things need phosphorus to function, along with other elements such as hydrogen, oxygen, carbon, nitrogen and sulphur. The phosphate ion, PO 4 3-, plays several essential roles in cells: it maintains the structure of DNA and RNA, combines with lipids to make cell membranes and transports energy within the cell through the molecule adenosine triphosphate (ATP).

But Felisa Wolfe-Simon, a geomicrobiologist and NASA Astrobiology Research Fellow based at the US Geological Survey in Menlo Park, California, and her colleagues report online today in Science1 that a member of the Halomonadaceae family of proteobacteria can use arsenic in place of phosphorus. The finding implies that "you can potentially cross phosphorus off the list of elements required for life", says David Valentine, a geomicrobiologist at the University of California, Santa Barbara.

Many science-fiction writers have proposed life-forms that use alternate elemental building blocks, often silicon instead of carbon, but this marks the first known case in a real organism. Arsenic is positioned just below phosphorus in the periodic table, and the two elements can play a similar role in chemical reactions. For example, the arsenate ion, AsO 4 3-, has the same tetrahedral structure and bonding sites as phosphate. It is so similar that it can get inside cells by hijacking phosphate's transport mechanism, contributing to arsenic's high toxicity to most organisms.

Element of surprise

Wolfe-Simon thought the parallels between the two elements could mean that despite its toxicity, arsenic was capable of performing phosphorus's job in the cell. Her search for an organism that would not just tolerate arsenic but make biological use of it took her to Mono Lake in eastern California. The 180-square-kilometre lake has an extremely high arsenic concentration, owing to arsenic-bearing minerals that wash down from nearby mountains.

Wolfe-Simon and her colleagues collected mud from the lake and added the samples to an artificial salt medium lacking phosphate but high in arsenate. They then performed a series of dilutions intended to wash out any phosphate remaining in the solution and replace it with arsenate. They found that one type of microbe in the mix seemed to grow faster than others.

The researchers isolated the organism and found that when cultured in arsenate solution it grew 60% as fast as it did in phosphate solution — not as well, but still robustly. The culture did not grow at all when deprived of both arsenate and phosphate.

When the researchers added radio-labelled arsenate to the solution to track its distribution, they found that arsenic was present in the cellular fractions containing the bacterium's proteins, lipids and metabolites such as ATP and glucose, as well as in the nucleic acids that made up its DNA and RNA. The amounts of arsenate detected were similar to those expected of phosphate in normal cell biochemistry, suggesting that the compound was being used in the same way by the cell.

The team used two different mass-spectrometry techniques to confirm that the bacterium's DNA contained arsenic, implying — although not directly proving —that the element had taken on phosphate's role in holding together the DNA backbone. Analysis with laser-like X-rays from a synchrotron particle accelerator indicated that this arsenic took the form of arsenate, and made bonds with carbon and oxygen in much the same way as phosphate.

"Our data are strongly suggestive of arsenic replacing phosphorus," says Wolfe-Simon, adding that if the relatively common Halomonadaceae microbe can do it, others probably can too. "It may be an indication of this whole other world nobody has seen," she says.

A world of possibilities

Mary Voytek, who heads NASA's astrobiology programme in Washington DC, agrees that the results are persuasive. "I think no single one of their measurements can prove" that arsenate is doing what phosphate normally would, she says, but taken together, "I will conservatively say that it's very hard to come up with an alternative explanation."

To be truly convincing, however, the researchers must show the presence of arsenic not just in the microbial cells, but in specific biomolecules within them, says Barry Rosen, a biochemist at Florida International University, Miami. "It would be good if they could demonstrate that the arsenic in the DNA is actually in the backbone," he said.

Also, he says, the picture is still missing an understanding of what exactly the arsenic–phosphorus switch means for a cell, says Rosen. "What we really need to know is which molecules in the cell have arsenic in them, and whether these molecules are active and functional," he says.

For example, if phosphate in ATP was exchanged for arsenate, would the energy-transfer reaction that powers a cell be as efficient? In metabolic processes in which arsenate would bind with glucose, would the bonds it forms — weaker than those of phosphate — be as effective? And phosphate groups bind to proteins modify their function, but would arsenate work as well?

"As a chemist, I'm obsessed with details," says Rosen. "I think future studies will really have to tie down how this organism does it."

Others held deeper reservations. "It remains to be established that this bacterium uses arsenate as a replacement for phosphate in its DNA or in any other biomolecule found in 'standard' terran biology," says Steven Benner, who studies origin-of-life chemistry at the Foundation for Applied Molecular Evolution in Gainesville, Florida.

Arsenate forms much weaker bonds in water than phosphate, that break apart on the order of minutes, he says, and though there might be other molecules stabilizing these bonds, the researchers would need to explain this discrepancy for the hypothesis to stand. Still, the discovery is "just phenomenal" if it holds up after further chemical analysis, Benner adds. "It means that many, many things are wrong in terms of how we view molecules in the biological system."

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In addition to questioning the long-held assumption that phosphate is absolutely required for life, the existence of the bacterium "provides an opportunity to really pick apart the function of phosphorus in different biological systems", notes Valentine. There may even be a way to use the arsenic-loving microbes to combat arsenic contamination in the environment, he adds.

Meanwhile, Wolfe-Simon and her colleagues agree that there is a lot more to be done. The first step is to see whether these or other bacteria replace phosphate with arsenic naturally, without being forced to do so in the lab, she says. The group also has plans to sequence the microbe's genome.

"We have 30 years of work ahead to figure out what's going on," says Wolfe-Simon.

In the light of various criticisms of the findings, Nature has posted a "follow-up":http://go.nature.com/4EQ18o story.