Cisbio eBook - 28

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

Organisms typically work with 64 codons. But
as Zhang noted, natural organisms have never
encountered codons that contain unnatural
bases. "Thus," he asserted, "these codons are
blank, free of any natural function and free
to be dedicated for unnatural amino acid
incorporation."

Semi-synthetic Escherichia coli producing green fluorescent
protein via decoding of an unnatural codon.

effectively inside a cell, said Yorke Zhang, a
graduate student working in the laboratory of
Floyd E. Romesberg, Ph.D., a professor of chemistry at The Scripps Research Institute in La Jolla,
CA. In experiments carried out at the Romesberg
laboratory, Zhang and colleagues created new
codons-combinations of three genetic letters
28 | GENengnews.com

In an article published November 30, 2017 in the
journal Nature,1 Zhang and colleagues demonstrated that two of the unnatural codons work in
the cell. The article's authors also indicated that
152 blank codons might be available to help with
synthesis of nonnatural proteins.
"It's likely that not all of [the new codons] work,"
Zhang admitted, "but I'm pretty confident that we
will have more codons that work that could ever be
practically used." The Romesberg lab, he continued,
has been working on unnatural base pairs and their
implications for nearly two decades. "In a sense,
we've just gotten started," he maintained.

Universal Expansion
While Zhang and colleagues have tackled
the challenge of creating codons by adding
nonnatural base pairs to E. coli, others are taking
a different approach. They're working with molecules already operating in the cell, particularly an
enzyme called aminoacyl tRNA synthetase (aaRS),
which attaches to tRNA that suppresses stop
codons.
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.  
Jodie Chin, PhD, jodie@scripps.edu

Adapted from an image taken by William B. Kiosses, Ph.D., wkiosses@scripps.edu

that typically correspond to a particular amino
acid or a signal that stops protein synthesis.



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