Biologists are close to reinventing the genetic code of life

John Bohannon in Science:

The term “life hacking” usually refers to clever tweaks that make your life more productive. But this week in Science, a team of scientists comes a step closer to the literal meaning: hacking the machinery of life itself. They have designed—though not completely assembled—a synthetic Escherichia coli genome that could use a protein-coding scheme different from the one employed by all known life. Requiring a staggering 62,000 DNA changes, the finished genome would be the most complicated genetic engineering feat so far. E. coli running this rewritten genome could become a new workhorse for laboratory experiments and a factory for new industrial chemicals, its creators predict. Such a large-scale genomic hack once seemed impossible, but no longer, says Peter Carr, a bioengineer at the Massachusetts Institute of Technology Lincoln Laboratory in Lexington who is not involved with the project. “It's not easy, but we can engineer life at profound scales, even something as fundamental as the genetic code.”

The genome hacking is underway in the lab of George Church at Harvard University, the DNA-sequencing pioneer who has become the most high-profile, and at times controversial, name in synthetic biology. The work takes advantage of the redundancy of life's genetic code, the language that DNA uses to instruct the cell's protein-synthesizing machinery. To produce proteins, cells “read” DNA's four-letter alphabet in clusters of three called codons. The 64 possible triplets are more than enough to encode the 20 amino acids that exist in nature, as well as the “stop” codons that mark the ends of genes. As a result, the genetic code has multiple codons for the same amino acid: the codons CCC and CCG both encode the amino acid proline, for example. Church and others hypothesized that redundant codons could be eliminated—by swapping out every CCC for a CCG in every gene, for instance—without harming the cell. The gene that enables CCC to be translated into proline could then be deleted entirely. “There are a number of 'killer apps'” of such a “recoded” cell, says Farren Isaacs, a bioengineer at Yale University, who, with Church and colleagues, showed a stop codon can be swapped out entirely from E. coli. The cells could be immune to viruses that impair bioreactors, for example, if crucial viral genes include now untranslatable codons.

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