Chemists expand genetic code of E. coli to produce 21st amino acid, giving it new abilities

Discussion in 'Biology & Genetics' started by paddoboy, Aug 12, 2020.

  1. paddoboy Valued Senior Member

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    https://phys.org/news/2020-08-chemists-genetic-code-coli-21st.html

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    Rice University researchers introduced noncanonical amino acid building blocks into proteins in living cells, pioneering a powerful tool for investigating and manipulating the structure and function of proteins. The resulting unnatural organism, a strain of Escherichia coli bacteria, is able to monitor low levels of oxidative stress. Credit: Xiao Lab/Rice University

    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.
    more at link............
    the paper:

    https://www.cell.com/chem/fulltext/...om/retrieve/pii/S2451929420303636?showall=tru

    Creation of Bacterial Cells with 5-Hydroxytryptophan as a 21st Amino Acid Building Block

    Summary
    While most organisms utilize 20 canonical amino acid building blocks for protein synthesis, adding additional candidates to the amino acid repertoire can greatly facilitate the investigation and manipulation of protein structures and functions. In this study, we report the generation of completely autonomous organisms with a 21st noncanonical amino acid, 5-hydroxytryptophan (5HTP). Like 20 canonical amino acids, 5-hydroxytryptophan can be biosynthesized in vivo from simple carbon sources and is subsequently incorporated into proteins in response to the amber stop codon. Using this unnatural organism, we have prepared a single-chain immunoglobulin variable fragment conjugated with a fluorophore and demonstrated the utility of these autonomous cells to monitor oxidative stress. The creation of this and other cells containing the 21st amino acid will provide an opportunity to generate proteins and organisms with novel activities, as well as to determine the evolutionary consequences of using additional amino acid buildings.
     
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  3. RainbowSingularity Valued Senior Member

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    pharmacological bio-availability application ?
    possibly useful for some type of chemo therapy tracer/marker/indicator ?
    (i can barely comprehend the basic concept[im hopeless with chem & bio] but that type of thing comes to mind)
     
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  5. Yazata Valued Senior Member

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    I think that the first people to accomplish this were Peter Schultz and his group at the Scripps Research Institute in San Diego.

    https://www.schultz.scripps.edu/research

    I wrote this post on another discussion board back in 2017:

    ***********************************************

    I was reading about this and thought that it was pretty extraordinary.

    As most of you probably know, proteins are made of amino acids and some 20 amino acids are coded for by DNA and are found in (Earth) life.

    What makes this a bit mysterious is the fact that there are far more amino acids than that, some 500 in total. So why are only this particular set of 20 coded for by DNA? Is it just fortuitous, an accident resulting from the original origin-of-life-events that just happened to produce a genetic coding mechanism for this particular 20? Has all of subsequent life built itself upon that narrow foundation?

    So the question arises, could synthetic DNA be engineered that codes for alternative amino acids that are not part of the favored 20? Would that DNA and the cells that contain it survive and sucessfully replicate?

    And more speculatively, could expanding the genome's amino acid vocabulary give these synthetic organisms new properties?

    I was just reading about work being done on these lines here:

    https://www.schultz.scripps.edu/research

    Peter Schultz writes:

    "The genetic codes of every known organism specify the same 20 amino acid building blocks using triplet codons generated from A, G, C and T. These twenty amino acids contain a limited number of functional groups including acids, amides, alcohols, basic amines and thiols. Is this the ideal number or would additional amino acids allow the generation of proteins or even entire organisms with enhanced properties?...

    ...To this end, we have developed a methodology that allows one to genetically encode novel amino acids, beyond the common twenty, in both prokaryotic and eukaryotic organisms."


    See also:

    https://en.wikipedia.org/wiki/Expanded_genetic_code

    https://en.wikipedia.org/wiki/Peter_G._Schultz

    "This is accomplished by screening libraries of mutant amino acyl tRNA synthetases for mutants which charge nonsense-codon tRNAs with the desired unnatural amino acid. The organism which expresses such a synthetase can then be genetically programmed to incorporate the unnatural amino acid into a desired protein in the usual way, with the nonsense codon now coding for the unnatural amino acid...

    More than seventy unnatural amino acids have been genetically encoded in bacteria, yeast, and mammalian cells, including photoreactive, chemically reactive, fluorescent, spin-active, sulfated, pre-phosphorylated, and metal-binding amino acids. This technology allows chemists to probe, and change, the properties of proteins, in vitro or in vivo, by directing novel, lab-synthesized chemical moieties specifically into any chosen site of any protein of interest."


    Don't be surprised if you see this work winning a Nobel prize sometime in the future.

    *****************************************

    And another 2017 post by me on the same subject

    *****************************************

    More news on this today.

    All DNA found in Earth organisms, from bacteria to human beings, has 4 bases: A,G,C and T. (Adenine, Guanine, Cytosine and Thymine.) Now the synthetic biology laboratory at the Scripps Research Institute referred to above has produced functional successfully reproducing bacteria with 6 DNA bases. The two new bases enable this artificially alien DNA to code for new amino acids that aren't part of the 20 normally found in Earth life.

    The difference between this new development and the post immediately above, is that earlier work was incorporating the novel amino acids by engineering unnatural transfer RNAs. Now they have not only written the ability to produce them into the cell's DNA itself, they have done it by adding to DNA's chemical alphabet in a way that isn't seen anywhere else in Earth life.

    Believe me, from a theoretical evolutionary molecular biological point of view, this is big.

    The MIT Technology Review opines:

    "...the alien germs growing in San Diego already hint that our Earth biology isn't the only one possible. It suggests that if life did evolve elsewhere, it might have done so using very different molecules... life as we know it my not be the only solution, and may not be the best one."

    https://www.technologyreview.com/s/609567/semi-synthetic-life-form-now-fully-armed-and-operational/

    Another news story

    https://cosmosmagazine.com/biology/four-dna-bases-good-six-better

    The lab's webpage

    http://www.scripps.edu/romesberg/publications.html#Alphabet

    The report is coming out in Nature, where the abstract says:

    "Here we report the in vivo transcription of DNA containing dNaM and dTPT3 into mRNAs with two different unnatural codons and tRNAs with cognate unnatural anticodons, and their efficient decoding at the ribosome to direct the site-specific incorporation of natural or non-canonical amino acids into superfolder green fluorescent protein."

    https://www.nature.com/articles/nature24659
     
    Last edited: Aug 14, 2020
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  7. paddoboy Valued Senior Member

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    Can you elaborate as simply as possible on the possible consequence of the above....
    Nice post by the way.
     
  8. Michael 345 New year. PRESENT is 72 years oldl Valued Senior Member

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