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Reconstituting ribosomes: Shown here is a parts list for creating a synthetic, self-replicating ribosome. Proteins are shown in purple, RNA in red, and DNA in blue. The list includes 54 ribosomal proteins, as well as RNA-based enzymes involved in protein production, and other molecules that interact with ribosomes.

Church and his team also want to use the ribosome to make a new class of proteins–those that are the mirror image of the proteins found in nature. Proteins and many other molecules have a “handedness,” or chirality, to their structure. Amino acids made in nature are almost exclusively left-handed. And just as a glove fits on only one hand, left-handed enzymes can only catalyze reactions of substrates with the correct handedness. This means that mirror-image molecules would be resistant to breakdown by regular enzymes, says Church. That could have important industrial applications, generating long-lasting enzymes for biofermentation, used to create biofuels and other products.

The pharmaceutical industry might also benefit from a method to make mirror-image molecules. Unlike biological synthesis, chemical synthesis produces a mixture of left- and right-handed molecules. But with many drugs–the most notorious example is thalidomide–one form is beneficial and the other harmful. It’s expensive to separate the two versions, so an efficient alternative that makes just the desired form from the start could be a boon to manufacturers. Church and Jewett have not yet made a mirror-image protein using their synthetic ribosome, but they say that it can be done just by tweaking a few molecules in the enzyme that joins amino acids into proteins.

The artificial ribosome also has much broader applications. It is a major step on the way to creating artificial life–a cell that can self-assemble and reproduce. Scientists want to create an organism from scratch both to better understand the inner workings of biology and to create new, highly engineerable life forms that can be employed to make new fuels, clean up toxins, or perform other useful functions.

In addition, the ribosome might solve major unanswered questions about the origins of life. “How did the first ribosomes or the equivalent structure evolve on the way to life as we know it? This is really a major gap in our understanding of the origin of life,” says Deamer. “If [Church] can manipulate parts to make a better or simpler version of the ribosome, it will teach us a lot about how ribosomes came to be.” And second, why does almost all life have a left-handed chirality? “It’s a mystery,” says Fred Blattner, a geneticist at the University of Wisconsin-Madison. “Did it just happen that way, or is there a reason we are not aware of?” With a left-handed ribosome, the answer to the question may soon be in reach.

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Credits: NY State Deparment of Health, George Church and Mike Jewett

Tagged: Biomedicine, DNA, RNA, cells, Harvard, George Church

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