“Shrink to grow” is a two-pronged business strategy where a company gets rid of unprofitable brands (“shrink”) to focus its resources on a few remaining or new brands (“grow”). Companies like P&G and Microsoft have used it, and a similar idea to “shrink to grow” is behind the George Church lab’s ongoing development of the synthetic bacteria rEcoli57. But while the executives at P&G were streamlining the number of brands they carry, the researchers in the Church lab are streamlining rEcoli57’s genetic code in order to more effectively expand it later.
One’s genetic code determines how information goes from DNA to proteins. More specifically, it defines how each codon – a triplet of nucleotides, the building blocks of DNA – codes for a specific amino acid in a protein sequence. For instance, the codon guanine-adenine-thymine (GAT) in Figure 1 codes for aspartic acid (Asp), while the codon adenine-adenine-thymine (AAT) codes for a different amino acid, in this case asparagine (Asn).
There are 20 common amino acids in organisms, but there isn’t one codon for each amino acid. Rather, 64 DNA triplets code for only 20 amino acids, and this redundancy is present in the genetic code of all organisms. Over the years many labs have exploited this redundancy, reassigning a redundant codon to a new, uncommon amino acid and thus expanding an organisms genetic code. Uncommon amino acids can add a lot of cool features to an organism, but for them to incorporate well into the genome, it helps to start with a clean slate. That clean slate is exactly what the Church lab is working towards with rEcoli57, a synthetic bacteria based on E. coli that uses 57 codons instead of the common 64.
The Church lab is using a patchwork-like method to develop rEcoli57: first they design the 57-codon DNA sequence on a computer and then small sequences of DNA that overlap one another are synthesized and assembled into larger pieces (~1/100th of a genome each). Eventually these pieces are patched together to generate the full, almost 4-million-nucleotide rEcoli57 genome. Before assembling the full genome, each individual piece is evaluated to see if the streamlined 57-codon genome has affected protein production and cell viability. Currently 63% of the pieces have been evaluated and a method for correcting harmful modifications is in place.
Pushing the boundaries of life is an exciting enough reason to take on the project of generating a 57-codon E. coli. But, for Matthieu Landon, one of the researchers on the project, rEcoli57 isn’t just about proving that the genetic code can be streamlined; it’s also about “decreasing the genetic code to increase it again” and creating the methodology to do so.
Special thanks to Matthieu Landon, a PhD candidate in the Systems Biology program at Harvard University and one of the researchers working on rEcoli57, for his time, help and multiple suggestions.
Design, synthesis and testing toward a 57-codon genome (Science) – not open access
“Radically rewritten” bacterial genome revealed (Nature)
By NIAID – E. coli Bacteria, CC BY 2.0 (via WikiCommons)