Early proteins may have sprouted under thirsty conditions

The primordial soup cooked up by UW–Madison’s John Yin is a thin one indeed: Besides an amino acid, it contains just copper and chloride.

Nonetheless, by simply drying this lean mixture and letting it incubate at 80 degrees Celsius, the UW–Madison chemical and biological engineering professor was able to link molecules of the amino acid together in twos and threes, a critical step on the path to making proteins.

Now appearing in the online edition of the journal Peptides, the study suggests that before cells or other biological systems evolved, chemical reactions taking place under dry conditions may have played a role in forming the earliest simple proteins.

“When we think about the origin of life, we always think about water,” says Yin, who conducted the research with graduate student Joseph Napier. “But in this case, the chemistry is facilitated by the absence of water. The essential chemistry depends on removing water.”

The study also defines the minimal conditions under which biological building blocks, in this case amino acids, can organize themselves into larger molecules – information engineers might one day use to design “smart” materials that can direct their own synthesis, repair themselves and even evolve.

“We would like to make materials that could develop new properties and respond to changes in the environment – this is currently the science fiction part,” Yin says. “But we know living systems can do it, and we want to mimic this to engineer those properties into inanimate materials.”

The proteins that make up living beings are composed of chains of 20 different amino acids. Each amino acid, in turn, contains an “amino” end and a “carboxyl” end, as well as a unique side chain – a chemical group that distinguishes it from the others.

Amino acids join when the carboxyl end of one bonds with the amino group of another. Important to Yin’s experiments, the paired amino acids must give up an oxygen atom and two hydrogen atoms (a molecule of water) for the bond to form.

Cells use an intricate complex of RNA and proteins to forge these bonds, while chemists achieve the same thing in a test tube by adding dehydrating reagents – chemicals that remove water in the vicinity of the bond to facilitate the connection. But in the environment of the early earth, biological catalysts and sophisticated reagents obviously didn’t exist.

“In prebiotic chemistry, we want to stay away from the more elegant chemistries that organic chemists use today,” says Yin. “So the questions become, ‘At the very beginning what reactants were around?’ ‘What sorts of chemistries were feasible?'”

Building on the work of earlier studies, Yin and Napier focused on solutions of the metal copper in the form of copper chloride, and the amino acid alanine. They chose alanine deliberately. Unlike the more complicated side chains of most of the other 19 amino acids, alanine’s side group is simple and essentially nonreactive. This ensured that any linkages observed by the engineers were the result of true bonds between the alanine molecules’ carboxyl and amino ends, rather than unintended connections between the side chains.

After mixing the reactants together in water, Yin and Napier dried the samples during a 10-hour period and let them incubate for up to 25 days. Within 13 hours, they detected both pairs and triplets of alanine molecules, known as dialanine and trialanine. Yields of dialanine increased steadily during the 25 days of the experiment, until they eventually constituted more than 10 percent of the original mixture. The team also found the reaction specifically required copper; other metals such as zinc, nickel and silver failed to link the molecules.

Yin believes the process works through the formation of reaction complexes between alanine and copper. As the mixture dries, copper organizes the reactive clusters and catalyzes the creation of bonds between adjacent alanine molecules. And much like the dehydrating agents of chemists, the loss of water from these mixtures also promotes bond formation.

From here, Yin plans to methodically build more information into the system and observe what new possibilities emerge at each step. For example, he could add a second amino acid B that bonds with his first amino acid A to form an A-B-A string. What if, Yin speculates, A-B-A happened to promote the formation of the A-B bond to make more A-B-A?

“If we can create conditions to produce more chemical diversity,” he says, “we have the potential at least to expand our capabilities for chemical synthesis.”