Scientists Create First Semi-Synthetic Organism That Stores And Retrieves Unnatural Information

Source: The Scripps Research Institute

Summary: Researchers have designed a first semi-synthetic organism that can store and retrieve genetic information which in future could help to produce new molecules for medical therapies.

Nearly 3.5 billion years ago, life on earth evolved to have 4 “letters” in its genetic code. The letters are the DNA bases – G (Guanine), C (Cytosine), A (Adenine) and T (Thymine) which give out the instructions for producing proteins in every organism on earth. But the researchers from The Scripps Research Institute have designed a first semi-synthetic organism that can store and retrieve genetic information which in future could help to produce new molecules for medical therapies. They created a semi-synthetic strain of bacterium, E. coli with two unnatural bases, called X and Y in its DNA and use these bases to instruct cells to generate a new protein. The study findings were published in the journal Nature.

decoding of an unnatural codon in a semi-synthetic organism

Schematic depicting the incorporation of a non-canonical amino acid (ncAA) into a protein via ribosomal decoding of an unnatural codon in a semi-synthetic organism Credit: Adapted from an image created by Dennis Sun, Mezarque Design

Until now all organisms used only four DNA bases to code for 20 amino acids (building blocks of proteins). With this new addition of X and Y, an organism could code for up to 152 new amino acids. They designed the part of X and Y to be hydrophobic, so they can only pair with each other and avoid accidental pairing with regular bases A, T, G, C. This showed that complementary hydrogen bonding doesn’t really bother cells as X and Y were successfully transcribed and translated. The researchers hope the new amino acids could become building blocks for new medicines. Scripps’ technology has been licensed by a biotech company, Synthorx Inc., co-founded by Romesberg, that aims to make novel protein-based drugs based on X and Y.

E. coli bacteria

This photo shows a semi-synthetic strain of E. coli bacteria that can churn out novel proteins. Scientists reported that they have expanded the genetic code of life and used man-made DNA to create this strain of bacteria. Credit: Bill Kiosses/The Scripps Research Institute

Prof. Floyd Romesberg said, “I would not call this a new lifeform—but it’s the closest thing anyone has ever made”, “This is the first time ever a cell has translated a protein using something other than G, C, A or T.”

More Information: Yorke Zhang et al, “A semi-synthetic organism that stores and retrieves increased genetic information”, Nature (2017). DOI:10.1038/nature24659

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