Editorial: The scary business of tinkering with life
A TOTALLY new genetic code has been devised, along with machinery that could make it a biological reality. It’s an advance that means living cells could be persuaded to make proteins with properties that have never been seen in the natural world.
More extraordinary still, it could eventually lead to the creation of new or “improved” life forms that incorporate these materials in their tissue – possibly even organisms with bulletproof bodies.
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In all existing life forms, the cell’s protein-making machinery reads the four chemical “letters” of DNA – called nucleotides – in triplets to make chains of amino acids. Each three-letter word embodies the code for a single amino acid or tells the cell to stop making a protein chain.
Not any more. at the University of Cambridge and his colleagues have redesigned the cell’s machinery so that it can also read the genetic code four letters at a time.
In this way, Chin’s team has boosted the number of amino acids that can be built into a protein from the 20 covered by the existing genetic code to 276. That’s because Chin’s new code creates 256 possible four-letter nucleotide words or “codons”, each of which can be assigned to an amino acid that doesn’t currently exist in living cells.
Many such amino acids have already been made by adding different chemical groups to the basic amino acid structure. Until now, the issue has been how to incorporate large numbers of them into proteins.
To tackle this problem, Chin’s team redesigned several pieces of the cell’s protein-building machinery, including ribosomes and transfer RNAs (tRNAs). Together, they read the genetic code and match it up to amino acids (see diagram). The redesigned ribosomes and tRNAs operate in parallel with existing machinery, so the cell’s normal protein translation machinery continues to work as normal. “It’s the beginning of a parallel genetic code,” says Chin.
Chin’s team then inserted two quadruplet codons into the gene that codes for the common protein calmodulin, and assigned an “unnatural” amino acid to each quadruplet. When they inserted the modified gene into E. coli, it produced a modified calmodulin protein, incorporating the two unnatural amino acids.
What makes the new amino acids especially interesting is that they react with each other to form a different kind of chemical bond from those that usually hold proteins together. In the modified calmodulin, they led to a completely new protein structure.
Changes in heat and acidity break normal bonds between amino acids, causing proteins to lose their 3D structure. This, for instance, is why egg white changes colour and texture when cooked: bonds in the albumen in the white break and reform, changing its physical properties.
“Can you watch a new form of life boot up? And can you get it to do things that natural biology can’t do?”
But the bonds between Chin’s new amino acids are more stable – and so could allow proteins to survive a much wider range of environments. One outcome might be a new class of drugs that can be swallowed without being destroyed by the acids in the digestive tract.
That’s just the beginning. In the longer term Chin’s research could lead to cells that produce entirely new polymers – with the strength of Kevlar, say. Organisms made of these cells could incorporate the stronger polymers and become stronger or hardier as a result.
The next step in this direction is to design more new tRNAs that can incorporate more unnatural amino acids into protein chains. Doing so should lead to the creation of whole new classes of materials, Chin says. And because they could be churned out by bacteria grown in large fermentation vats, it would probably be a cheaper way of producing them than chemical synthesis.
“It’s a very impressive advance that opens up new theoretical horizons in synthetic biology,” says genomics pioneer and synthetic biologist Craig Venter, who heads his own institute in Rockville, Maryland.
Farren Isaacs of Harvard Medical School in Boston cautions that the new polymers may interfere with existing cellular processes. But as long as this does not prove an insuperable problem, Chin’s achievement could pave the way for the creation of complex life forms with bizarre new properties.
“If you have a cell with DNA, RNA, proteins and a new class of polymers, can you watch a new form of life boot up with that system embedded in it?” ponders Chin. “And can you get that organism to do things that natural biology can’t do because of the limited set of polymers that it can make?”
Editorial: The scary business of tinkering with life
Journal reference:
A shorter version of this article appeared on newscientist.com on Sunday
