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Prebiotic Amino Acids as Asymmetric Catalysts

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Science  20 Feb 2004:
Vol. 303, Issue 5661, pp. 1151
DOI: 10.1126/science.1093057

The exogenous delivery of cometary and asteroidal material is observed today and undoubtedly has showered the Earth through its prior history (1). Because carbonaceous meteorites contain amino acids displaying asymmetry that, if not as extensive, has the same sign (L) as terrestrial amino acids (2), it is reasonable to ask whether these chiral compounds, acquired upon delivery to the early Earth, could have played a role in the origin of homochirality by transferring their asymmetry to other prebiotic building blocks, such as sugars.

To assess this possibility, we examined the catalytic influence of two nonracemic amino acids, alanine and isovaline, on a water-based prebiotic model of sugar syntheses from glycolaldehyde and formaldehyde (3). Alanine is a common protein amino acid and isovaline is the most abundant chiral amino acid in meteorites. Results show a catalytic asymmetric effect.

Two series of sugar syntheses were studied; in one, the reagent was glycolaldehyde alone, and in the second, formaldehyde and glycolaldehyde were reacted in equal amounts. Reactions were carried out in an aqueous triethylammonium acetate buffer (pH 5.4 at 50°C) in the presence of either amino acid in various enantiomeric excesses (ee). The duration was 10 hours to limit sugar production to the four-carbon species, threose and erythrose, which are formed by aldol condensation of two glycolaldehyde molecules. Reaction products were analyzed by gas chromatography-mass spectrometry, using a chiral phase that separated all tetrose enantiomers (fig. S1).

The catalyzed aldol condensation of glycolaldehyde in water produces tetroses whose chiral configuration is affected by the chirality of the amino acid catalyst (Fig. 1); ee are largest for threose produced by enantiomerically pure isovaline and decrease upon decrease of catalyst ee. The asymmetric effect is still seen at levels of catalyst ee found in meteorites (table S1) and occurs at the C-2 carbon that acquires the same configuration in both threose and erythrose. (Although tetroses contain two asymmetric carbons, C-2 and C-3, only the C-3 configuration dictates the D-, and L-designation.)

Fig. 1.

Effect of amino acid catalyst ee on the asymmetric synthesis of threose and erythrose from glycolaldehyde. S-ivaline is equivalent to l-2-amino 2-methyl butyric acid.

This asymmetric effect at the C-2 carbon is consistent with an aldol condensation involving the formation of a chiral Schiff base (imine) intermediate between the aldehyde of one glycolaldehyde molecule and the catalyst amino acid, followed by stereoselective addition of a second glycolaldehyde and hydrolysis of the imine (fig. S2). Hydrogen bonding between the carboxyl anion, the nitrogen, and the hydrogen from the glycolaldehyde C-2–hydroxyl may affect the configuration of this carbon upon the addition of the second aldehyde. Intermediates with more hindered rotation, like one containing alpha-substituted isovaline, would be expected to have a stronger asymmetric effect, as demonstrated by the 60% larger asymmetry transfer by isovaline than alanine.

When glycolaldehyde and formaldehyde were reacted in equal amounts, the catalysts' chirality also influenced the chiral yield of the tetrose products. As observed for glycolaldehyde alone, catalysis by isovaline had a stronger effect than alanine on product chirality. In both sets of syntheses, threose was the dominant product; erythrose was produced in lower yield and with reduced ee. Catalysis by proline, which has been observed in related reactions involving imine intermediates in organic solvents (4), was not seen under our reaction conditions.

The study has prebiotic plausibility. Both aldehydes we used could have been generated on the early Earth. Moreover, they are the substrates of a sugar-based model of biogenesis in which amino acids serve as catalysts and, in turn, are generated as end products. These reactions occur in water, which we must assume was part of any prebiotic environment that was favorable to life processes.

One of the obstacles in developing chiral homogeneity in prebiotic scenarios is the ease with which amino acids and sugars racemize in water (5). However, the amino acid isovaline is stereochemically stable because it lacks a hydrogen on the alpha carbon, the easy removal and random reacquisition of which allow interconversion between chiral configurations. Because isovaline is found in meteorites with ee up to 15%, an extended supply of the amino acid during the impact period of the early Earth could have provided a continuous and unique chiral influence in prebiotic sugar syntheses.

In view of the difficulty in postulating the de novo prebiotic formation of such complex molecules as DNA and RNA (6), several studies have explored the possibility of simpler polymers that would be based on molecules more easily synthesized under prebiotic conditions that still perform RNA-like functions. A series of such analogs have been described in which the sugar phosphate backbone contains threose instead of ribose (7). These threofuranosyl oligonucleotides, TNAs, form stable double helices both with each other and complementary to RNA and DNA. That such a tetrose was readily formed in our study with asymmetry and under likely early Earth conditions of endogenous and/or exogenous delivery of material, may suggest a pathway of molecular evolution in which extraterrestrial asymmetry provided the initial induction toward homochirality.

Supporting Online Material

www.sciencemag.org/cgi/content/full/303/5661/1151/DC1

Table S1

Figs. S1 and S2

References and Notes

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