Cisbio eBook - 29

Trends in Protein-Protein Interactions Research | Life's Code Accepts New Characters

Right now, with this approach, each non-natural
amino acid must be genetically encoded using
two distinct platforms, one for bacterial cells
and the other for eukaryotic cells. Accommodating two platforms is laborious, Dr. Chatterjee
complained.
Dr. Chatterjee and colleagues have been working
on an easier way. Their idea is to take advantage
of an E. coli strain in which one of the native
agars-tRNA pairs is functionally replaced with a
eukaryotic-archaeal counterpart. The replaced
pair can then be reintroduced into E. coli to get its
genetic code to produce nonnatural amino acids.
Because the pair originated in bacteria, it can also
be used to expand the genetic code of eukaryotes, the team reported in a paper published
February 13, 2017 in the journal Nature Chemical
Biology.2
"Our strategy will enable the development
of additional 'universal' aaRS-tRNA pairs," the
scientists reported. They also noted that their

29 | GENengnews.com

technique should enable genome engineers to
incorporate multiple, distinct nonnatural amino
acids into proteins in both eukaryotes and
bacteria. That opens the door for using synthetic
biology to accomplish a variety of tasks, including
the probing of protein-protein interactions
and the development of viruses that can home
in on and help kill cancer cells, explained Dr.
Chatterjee.

Chromosome by Chromosome
Inserting unnatural base pairs into cells and
tinkering with tRNA enzymes is not the only
way to transform codons. Another way to do it
is to completely rewrite the genetic code of an
organism. Harvard geneticist George Church,
Ph.D., and colleagues have been doing just that
with E. coli; they are now generating a code for
the bacterium that uses 57 codons, rather than
the standard 64. With seven codons removed
from E. coli's code, the researchers can reintegrate the string of letters into the cell so that they
introduce nonnatural amino acids into proteins
instead.

Something similar is being done with brewer's
yeast (Saccharomyces cerevisiae). So far, scientists
have stripped the yeast genome to its essentials,
making the eukaryote's code more stable and
easier to engineer.
"By building the genome from scratch, we're
testing the very foundation of biological knowledge," stated Leslie Mitchell, Ph.D., a geneticist
who works in the laboratory of Jef D. Boeke, Ph.D.,
director of the Institute for Systems Genetics at
New York University's Langone Medical Center.
Dr. Mitchell and colleagues have been designing
the new yeast genome chromosome by chromosome. In each chromosome, the scientists have
removed repetitive code and introduced loxPsym
sites to the ends of all nonessential genes. This
allows for a random shuffling of genes, the way
a dealer shuffles cards, Dr. Mitchell explained.
The addition of loxPsym markers, she continued,
could lead to the design of yeast strains that
make more ethanol, endure high temperatures,
or survive in other extreme environments.


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