Programmed bacteria have something extra

Date:
August 12, 2020
Source:
Rice University
Summary:
Chemists expand the genetic code of Escherichia coli bacteria to
produce a synthetic building block, a 'noncanonical amino acid'
that makes it a living indicator for oxidative stress. The research
is a step toward designed cells that detect disease and produce
their own drugs.



FULL STORY ==========================================================================
Rice University chemist Han Xiao and his team have successfully expanded
the genetic code of Escherichia coli bacteria to produce a synthetic
building block, a "noncanonical amino acid." The result is a living
indicator for oxidative stress.


==========================================================================
The work, they say, is a step toward technologies that will allow the generation of novel proteins and organisms with a variety of useful
functions.

Their study appears in the Cell Press journal Chem.

Amino acids are the building blocks of DNA. In general, organisms need
only 20 of them to program the entire set of proteins necessary for
life. But Xiao, with the help of a $1.8 million National Institutes
of Health grant, set out to see how a 21st amino acid would enable the
design of "unnatural organisms" that serve specific purposes.

The new study does just that by engineering bacteria to produce the extra
amino acid, called 5-hydroxyl-tryptophan (5HTP), which appears naturally
in humans as a precursor to the neurotransmitter serotonin, but not in
E. coli. The novel production of 5HTP prompts the bacteria to produce
a protein that fluoresces when the organism is under metabolic stress.

"The process requires a lot of interdisciplinary techniques," Xiao
said. "In this study, we combined synthetic chemistry, synthetic biology
and metabolic engineering to create a strain that synthesizes and encodes
a 21st noncanonical amino acid, and then uses it to produce the desired protein." Xiao said programming the autonomous unnatural bacteria was a three-step process: First, the researchers led by graduate student Yuda
Chen created bioorthogonal translational machinery for the amino acid,
5HTP. Second, they found and targeted a blank codon -- a sequence in
DNA or RNA that doesn't produce a protein -- and genetically edited it
to encode 5HTP. Third, by grafting enzyme clusters from other species
into E. coli, they gave the bacteria the ability to produce 5HTP.



========================================================================== "These 5HTP-containing proteins, isolated from the programmed bacteria,
can be further labeled with drugs or other molecules," Xiao said. "Here,
we show the strain itself can serve as a living indicator for reactive
oxygen species, and the detection limit is really low." While researchers
have reported the creation of more than 200 noncanonical amino acids to
date, most of them cannot be synthesized by their host organisms. "This
has been an ongoing field for decades, but previously people focused on
the chemical part," Xiao said. "Our vision is to engineer whole cells
with the 21st amino acid that will let us investigate biological or
medical problems in living organisms, rather than just dealing with
cells in the lab.

"Moving this technology to the host species eliminates the need to
inject artificial building blocks into an organism, because they
can synthesize and use it on their own," he said. "That allows us to
study noncanonical amino acids at a higher, whole organism level."
Ultimately, the researchers hope customized building blocks will allow
targeted cells, like those in tumors, to make their own therapeutic
drugs. "That's an important future direction for my lab," Xiao said. "We
want cells to detect disease, make better medicines and release them in
real time. We don't think that's too far away." Co-authors of the paper
are Rice postdoctoral fellows Juan Tang, Lushun Wang and Zeru Tian, undergraduate student Adam Cardenas and visiting scholar Xinlei Fang,
and Abhishek Chatterjee, an assistant professor of chemistry at Boston
College. Xiao is the Norman Hackerman-Welch Young Investigator and an
assistant professor of chemistry.

The Cancer Prevention and Research Institute of Texas, the Robert A. Welch Foundation, a John S. Dunn Foundation Collaborative Research Award and
a Hamill Innovation Award supported the research.


========================================================================== Story Source: Materials provided by Rice_University. Note: Content may
be edited for style and length.


========================================================================== Journal Reference:
1. Yuda Chen, Juan Tang, Lushun Wang, Zeru Tian, Adam Cardenas,
Xinlei Fang,
Abhishek Chatterjee, Han Xiao. Creation of Bacterial Cells with 5-
Hydroxytryptophan as a 21st Amino Acid Building Block. Chem, 2020;
DOI: 10.1016/j.chempr.2020.07.013 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200812161331.htm

--- up 4 weeks, 1 hour, 55 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1337:3/111)