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Chemical bond shields extreme microbes from poison
Molecular structure explains how ‘arsenic life’ bacteria rely on phosphate instead
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Molecular structure explains how ‘arsenic life’ bacteria rely on phosphate instead

By Alexandra Witze

Web edition: October 3, 2012
Print edition: November 3, 2012; Vol.182 #9 (p. 14)

Hardy bacteria that live in an arsenic bath survive in part by keeping poison from entering their cells, scientists have found. Just one tiny tweak in a hydrogen bond is enough to let the microbes pick out the phosphate they need to build their DNA — while keeping the arsenic out.

The work helps explain how famous bacteria in the arsenic-rich waters of Mono Lake, Calif., manage to live there without incorporating arsenic into their DNA, as a controversial 2010 paper had claimed (SN: 2/25/12, p. 10).

“It goes to show that life will find a way,” says Matthew Pasek, a geochemist at the University of South Florida who was not involved in the new study.

The discovery may also open new ways to deliver substances into a cell that are wanted, like drugs, while keeping unwanted stuff out. “The best way of avoiding poison is not to take it, and this is like the first defense mechanism,” says Mikael Elias, a biochemist at the Weizmann Institute of Science in Rehovot, Israel. He and his colleagues describe the finding online October 3 in Nature.

Mono Lake contains a witch’s brew of chemicals, yet a strain of Halomonas bacteria somehow manages to thrive there. The original “arsenic life” paper contended that the strain took up arsenate (a combination of arsenic and oxygen) in place of phosphate, the structurally similar chemical that forms the backbone of DNA in living organisms.

Elias had been studying the class of proteins that cells use to pull in phosphate, and suspected that Halomonas somehow fishes out the tiny bits of phosphate available from a sea of arsenate. So he and his colleagues examined the structures of five proteins, including two from the Mono Lake strain of Halomonas, that pull phosphate from the environment into cells.

All the proteins contain a particular hydrogen bond that latches onto phosphate (and arsenate). But structurally, that bond is slightly different in the Halomonas protein thought to be most responsible for choosing phosphate over arsenate. “It’s really a tiny difference, but it has a big consequence,” says Elias. “Basically with phosphate this bond is almost perfect” — but with the slightly larger arsenate the bond is much harder to make. That difference lets Halomonas take up phosphate molecules about 4,500 times as efficiently as it takes up arsenate, the team found. The other proteins tested all pick out phosphate over arsenate, but not nearly as dramatically.

Other structurally similar molecules, such as one based on vanadium, also compete with phosphate for getting into cells, says Pasek. The new work might help explain the great evolutionary mystery of why phosphate usually triumphs. 

The original arsenic-life paper reported that the Halomonas strain grew in the presence of arsenate alone. But some tiny amount of phosphate must have been present in that mix, scientists suspect.

“The new results add to the growing evidence that the earlier claim … was indeed incorrect,” says Tony Hunter, a biologist at the Salk Institute for Biological Studies in La Jolla, Calif.

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M. Elias et al. The molecular basis of phosphate discrimination in arsenate-rich environments. Nature. doi:10.1038/nature11517.

T.J. Erb et al. GFAJ-1 is an arsenate-resistant, phosphate-dependent organism. Science, Vol. 337, July 27, 2012, p. 467. doi: 10.1126/science.1218455. [Go to]

M.L. Reaves et al. Absence of detectable arsenate in DNA from arsenate-grown GFAJ-1 cells. Science, Vol. 337, July 27, 2012, p. 470. doi: 10.1126/science.1219861. [Go to]

F. Wolfe-Simon et al. A bacterium that can grow by using arsenic instead of phosphorus. Science, Vol. 332, June 3, 2011, p. 1163. doi: 10.1126/science.1197258. [Go to]


R. Ehrenberg. Arsenic-based life gets even more toxic. Science News Online, July 9, 2012. [Go to]

R. Ehrenberg. Arsenic-based life finding fails follow-up. Science News, Vol. 181, February 25, 2012, p. 10. Available online: [Go to]

R. Ehrenberg. Bacterium grows with arsenic. Science News, Vol. 179, January 1, 2011, p. 5. Available online: [Go to]

Comments (1)

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  • Chemistry matters - apparently to a lesser extent for desdendants of communication and anthropology theory

    Dear Aexandra Wiitze,

    I wonder why nearly everybody, during and in the aftermath of this perpetuated hype, circumvents a clear-cut argumentation, using his or her chemical education. It is unnecessary to look for highly exclusive phosphate transporters, because arsenate is, by its intrinsic physicochemical nature, highly unlikely to compete with phosphate for incorporation into DNA or into energy transducing analogues like ATP. There are at least two distinct phosphate transporter systems known, only one of them showing the extremely exclusive fit of phosphate into an appropriate binding site. But it is not necessary to argue with specificity of anion binding, because the decisive item is kinetic stability of the functional arsenate-analogues in the highly aqueous system of bacteria or higher organisms. Arsenate diester-anions cannot be, by chemical grounds, as stable as their phosphate diester-anions, the same for di- or tri-arsenates of whatever constitution. This is because the actual electronegativity of As(V) in arsenate is significantly higher than for P(V) in phospate (the Allred-Rochow EN values are 2,20 vs. 2.06, resp). As a consequence, the central atom in phosphate is much stronger shielded against nucleophilc attack by water molecules, by the partial charges on each of the oxygen ligands, compared to the central atom in arsenate. Instead of being an "anomaly" of the general trend of electronegativity for the p-block elements, this is the consequence of the well known 3-d orbital contraction of the first row of the d-block elements in the periodic system. In the case of phosphate- versus arsenate-incorporation for genetically and energetically relevant molecules, it would have been possible for every chemically educated science graduate to predict ab initio, from first principles, that the subject would immediately deflate into a non-issue! There has never been a competition between phosphate and arsenate because there is no need to exclude an arsenate precursor - the kinetic stability of functional arsenate analogues against hydrolysis is of the order of a thousand to a million less than of the respective phosphate derivatives. Take it exo- or esoterically: Electronegativity matters, there is neither matter nor need for "tailored" molecules, but a hint to the molecularly based singularity of life. Nature did not take a choice. Out there is but one chemical functionality to built up genetical storage and energy transducer molecules, as long as it has to work in aqueous systems, throughout universe.
    Marcus Wolf Marcus Wolf
    May. 21, 2013 at 8:47pm
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