Yorke Zhang, Jerod L. Ptacin, Emil C. Fischer, Hans R. Aerni, Carolina E. Caffaro, Kristine San Jose, Aaron W. Feldman, Court R. Turner & Floyd E. Romesberg

Since at least the last common ancestor of all life on Earth, genetic information has been stored in a four-letter alphabet that is propagated and retrieved by the formation of two base pairs. The central goal of synthetic biology is to create new life forms and functions, and the most general route to this goal is the creation of semi-synthetic organisms whose DNA harbours two additional letters that form a third, unnatural base pair. Previous efforts to generate such semi-synthetic organisms culminated in the creation of a strain of Escherichia coli that, by virtue of a nucleoside triphosphate transporter from Phaeodactylum tricornutum, imports the requisite unnatural triphosphates from its medium and then uses them to replicate a plasmid containing the unnatural base pair dNaM–dTPT3. Although the semi-synthetic organism stores increased information when compared to natural organisms, retrieval of the information requires in vivo transcription of the unnatural base pair into mRNA and tRNA, aminoacylation of the tRNA with a non-canonical amino acid, and efficient participation of the unnatural base pair in decoding at the ribosome. Here we report the in vivo transcription of DNA containing dNaM and dTPT3 into mRNAs with two different unnatural codons and tRNAs with cognate unnatural anticodons, and their efficient decoding at the ribosome to direct the site-specific incorporation of natural or non-canonical amino acids into superfolder green fluorescent protein. The results demonstrate that interactions other than hydrogen bonding can contribute to every step of information storage and retrieval. The resulting semi-synthetic organism both encodes and retrieves increased information and should serve as a platform for the creation of new life forms and functions.

This entry was posted in human being. Bookmark the permalink.

2 Responses to Yorke Zhang, Jerod L. Ptacin, Emil C. Fischer, Hans R. Aerni, Carolina E. Caffaro, Kristine San Jose, Aaron W. Feldman, Court R. Turner & Floyd E. Romesberg

  1. shinichi says:

    A semi-synthetic organism that stores and retrieves increased genetic information

    by Yorke Zhang, Jerod L. Ptacin, Emil C. Fischer, Hans R. Aerni, Carolina E. Caffaro, Kristine San Jose, Aaron W. Feldman, Court R. Turner & Floyd E. Romesberg

    Nature volume 551, pages 644–647 (30 November 2017)

    https://www.nature.com/articles/nature24659

  2. shinichi says:

    Artificial life breakthrough after scientists create new living organism using synthetic DNA

    The organism can store and retrieve man-made genetic information

    by Julie Steenhuysen

    https://www.independent.co.uk/news/science/artificial-life-synthetic-dna-scientists-living-organisms-create-scripps-research-institute-floyd-a8083966.html

    In a major step toward creating artificial life, US researchers have developed a living organism that incorporates both natural and artificial DNA and is capable of creating entirely new, synthetic proteins.

    The work, published in the journal Nature, brings scientists closer to the development of designer proteins made to order in a laboratory.

    Previous work by Floyd Romesberg, a chemical biologist at the Scripps Research Institute in La Jolla, California, showed that it was possible to expand the genetic alphabet of natural DNA beyond its current four letters: adenine(A), cytosine(C), guanine (G) and thymine(T).

    In 2014, Romesberg and colleagues created a strain of E. coli bacteria that contained two unnatural letters, X and Y.

    In the latest work, Romesberg’s team has shown that this partially synthetic form of E. coli can take instructions from this hybrid genetic alphabet to make new proteins.

    “This is the first time ever a cell has translated a protein using something other than G, C, A or T,” Romesberg said.

    Although the actual changes to the organism were small, the feat is significant, he said in a telephone interview. “It’s the first change to life ever made.”

    It’s a goal Romesberg has been working toward for the past 20 years. Creating new forms of life, however, is not the main point. Romesberg is interested in using this expanded genetic alphabet to create new types of proteins that can be used to treat disease.

    In 2014, he formed a company called Synthorx Inc, which is working on developing new protein-based treatments.

    “A lot of proteins that you want to use as drugs get cleared in the kidney very quickly,” Romesberg said. The new system would allow scientists to attach fat molecules to drugs to keep them in the body longer.

    Romesberg is aware that the creation of semi-synthetic organisms might raise concerns of hybrid life forms spreading beyond the lab, but the system they used makes such an escape unlikely.

    For example, in natural DNA, base pairs are attracted to each other through the bonding of hydrogen atoms. Romesberg’s X and Y bases are attracted through an entirely different process, which prevents them from accidentally bonding with natural bases.

    And because cells cannot make their own X and Y without the addition of certain chemicals, the semi-synthetic organisms cannot live outside of a laboratory.

    “They can’t escape,” Romesberg said. “There’s no ‘Jurassic Park’ scenario.”

Leave a Reply

Your email address will not be published.