Monday, July 03, 2023

How scientists are hacking the genetic code to give proteins new powers

Recommendable! A nice overview article! Amazing stuff!

This is only the beginning of human made evolution taking over slow natural evolution!

"... Amino acids are the building blocks of proteins, which do most of the heavy lifting in the cell; their side-chains govern protein folding, interactions and chemical activities. By limiting the available side chains, nature effectively restricts the kinds of reaction that proteins can perform.
As a doctoral student in the 1980s, Peter Schultz found himself wondering why nature had restricted itself in this way — and set about trying to circumvent this limitation. Several years later, as a professor at the University of California, Berkeley, Schultz and his team managed to do so by tinkering with the machinery of protein synthesis. ...
Scientists have also moved beyond E. coli to hack the genetic codes of nematode worms, fruit flies, plants and even mice. ...
Proteins typically interact with other molecules through relatively weak, non-covalent interactions, but covalent bonding could enhance their potency ... In 2020, ... team incorporated the non-canonical amino acid fluorosulfate-L-tyrosine (FSY) into PD-1, an immune checkpoint protein that helps to rein in the body’s immune response, to create an anti-tumour drug. Typically, the interaction between PD-1 on T cells, and PD-L1 on tumour cells, dampens the immune response, allowing the tumour to escape immune surveillance. When ... team injected the FSY-containing PD-1 into mice engrafted with human cancer cells, the protein formed an irreversible covalent bond with PD-L1, causing the tumours to shrink ...
In a 2021 study, ... team reported engineering cells that, in the presence of the synthetic amino acid O-methyl tyrosine, express insulin ...
By replacing all instances of a given codon for a synonymous one and removing the machinery that uses the original codon, researchers can render the cell effectively immune to foreign DNA — including pathogens. ...
Another group ... applied a similar ‘genetic firewall’ approach to create phage-resistant bacteria ...
Researchers can also use a modified genetic code to create polymers. In 2021, ... team hacked the genetic code to synthesize short polymers, and even an artificial circular structure called a macrocycle, in E. coli. Now, ... to push this technology further to create cell factories that can churn out entirely new polymers, such as plastics. ...
Besides codon reassignment, researchers can also increase the number of available protein building blocks by expanding the nucleic acid alphabet from four bases to six, thus increasing the number of possible triplet codons to 216. In 2014, a team ... reported creating a bacterial strain with a six-base genetic alphabet that could successfully replicate. The group subsequently demonstrated that these cells could use their expanded DNA to produce proteins containing non-canonical amino acids ...
Another approach is to expand the length of a codon from three bases to four, thus increasing the number of possible codons to 256. This requires modifying multiple pieces of the translation machinery, including the ribosome. ...
Some researchers are attempting more extreme alterations. These include backbone modifications — creating so-called β- or γ-amino-acids (as opposed to α-amino-acids, which are found in nature), or amino acids that are reverse mirror images of standard amino acids. Polymers built from either type of building block would probably be highly stable, because typical protein-degrading machinery would not be able to recognize them. ..."

How scientists are hacking the genetic code to give proteins new powers By modifying the blueprint of life, researchers are endowing proteins with chemistries they’ve never had before.



No comments: