Rewriting the genetic code of bacteria to open the "gate" to new drug research

Rewriting the genetic code of bacteria to open the "gate" to new drug research

Rewriting the genetic code of bacteria to open the "gate" to new drug research Rewriting the genetic code of bacteria to open the "gate" to new drug research

All living things on earth are composed of 20 different combinations of amino acids to form proteins
.

In order to add new amino acids to this composition, scientists have redesigned genes and other protein construction mechanisms, resulting in proteins with unique chemical properties that can be used to make drugs

Now, researchers have opened a "gate" that can do more: Extensive rewriting of a bacterial genome can add multiple new amino acids to a protein
.

This work may open up new ways for the synthesis of antibiotics and anti-tumor drugs

"This paper left a deep impression on me
.

" said Chang Liu (transliteration), a synthetic biologist at the University of California, Irvine.

This effort has been going on for decades
.

An early method of making "design proteins" was to "occupy" the cellular components that make proteins and insert unnatural amino acids

RNA is interpreted as a series of three-letter words called codons, most of which code for one of the 20 natural amino acids inserted into proteins
.

But because there are 64 three-letter codons, there will be repetitions

Initially, the researchers inserted the unnatural amino acid by letting the cellular machinery add an amino acid when it saw a specific stop codon
.

Jason Chin, a synthetic biologist at the Molecular Biology Laboratory of the American Medical Research Council, said that although this method has become more complicated, under normal circumstances, each protein can still only insert one amino acid

To add more codons, Chin and colleagues tried to reuse two of the six codons normally encoded for serine
.

In a 2019 study, researchers used the CRISPR-Cas9 gene editing tool to create an E.

This reuse is what Chin and colleagues are now doing
.

Using Syn61, the scientists deleted molecular genes called transfer RNAs (tRNAs), which can recognize UGC and UCA and insert serine into growing proteins

Abhishek Chatterjee, a synthetic biologist at Boston College, said: "It does have an impact
.
" These changes have allowed Chin and colleagues to string new amino acids into a series of ring structures, very similar to existing antibiotics and antitumor drugs
.
Because there are dozens of different unnatural amino acids to choose from, countless combinations can be inserted in this way
.
Chatterjee said this opens the door to the creation of a potentially large "library" of new drugs
.

The new drug "library" opened the door
.

Chin added that researchers can also extend this strategy to reuse other redundant codons, adding more new amino acids and more chemical diversity to the mix
.

Perhaps equally interesting, Liu Chang said, what the large-scale genome changes mean to the virus that normally infects E.
coli
.
In 2013, researchers reported that the stop codon of recombinant E.
coli may disrupt the ability of the virus to replicate
.
This is because viruses rely on the natural codons of E.
coli to make functional proteins
.
This strategy is not foolproof in preventing viral infections, because stop codons do not appear often, and some viruses can evolve around these changes
.

But viruses usually need to contain more serine in each protein
.
Since the modified Syn61 no longer inserts serine when its protein construction mechanism reads UCG or UCA codons, the virus cannot allow Syn61 to construct effective viral proteins, thereby preventing them from replicating in bacterial cells
.

"This seems to be more robust than the previous method
.
" Liu Chang said
.
He added that this could be a boon for biotech companies that want to protect engineered organisms that produce drugs or other valuable chemicals
.
(Source: Feng Weiwei, China Science News)

Related paper information: https://doi.
org/10.
1126/science.
abg3029

https://doi.
org/10.
1126/science.
abg3029