Editing Genetic code (section)

=== Expanded genetic codes (synthetic biology) ===
{{Main|Expanded genetic code}}
{{See also|Nucleic acid analogues}}

In a broad academic audience, the concept of the evolution of the genetic code from the original and ambiguous genetic code to a well-defined ("frozen") code with the repertoire of 20 (+2) canonical amino acids is widely accepted.<ref>{{Cite book| title = The book at the Wiley Online Library
| doi = 10.1002/3527607188
| isbn = 9783527312436
|last1 = Budisa|first1 = Nediljko| date = 2005-12-23
}}</ref>
However, there are different opinions, concepts, approaches and ideas, which is the best way to change it experimentally.{{Clarify|reason=are the opinions differing on "which one method is the best to change the experiments"?|date=February 2025}} Even models are proposed that predict "entry points" for synthetic amino acid invasion of the genetic code.<ref>{{cite journal
| last1 = Kubyshkin | first1 = V.
| last2 = Budisa | first2 = N.
| year = 2018
| title = Synthetic alienation of microbial organisms by using genetic code engineering: Why and how?
| journal = Biotechnology Journal
| volume = 12
| issue = 8
| pages = 16000933
| doi = 10.1002/biot.201600097
| pmid = 28671771
}}</ref>

Since 2001, 40 non-natural amino acids have been added into proteins by creating a unique codon (recoding) and a corresponding transfer-RNA:aminoacyl&nbsp;– tRNA-synthetase pair to encode it with diverse physicochemical and biological properties in order to be used as a tool to exploring [[protein structure]] and function or to create novel or enhanced proteins.<ref name="XieSchultz2005">{{cite journal | vauthors = Xie J, Schultz PG | title = Adding amino acids to the genetic repertoire | journal = Current Opinion in Chemical Biology | volume = 9 | issue = 6 | pages = 548–54 | date = December 2005 | pmid = 16260173 | doi = 10.1016/j.cbpa.2005.10.011 }}</ref><ref name="pmid19318213">{{cite journal | vauthors = Wang Q, Parrish AR, Wang L | title = Expanding the genetic code for biological studies | journal = Chemistry & Biology | volume = 16 | issue = 3 | pages = 323–36 | date = March 2009 | pmid = 19318213 | pmc = 2696486 | doi = 10.1016/j.chembiol.2009.03.001 }}</ref>

H. Murakami and M. Sisido extended some codons to have four and five bases. [[Steven A. Benner]] constructed a functional 65th (''[[in vivo]]'') codon.<ref name="isbn0-387-22046-1">{{cite book|first=Matthew |last=Simon | name-list-style = vanc | title = Emergent Computation: Emphasizing Bioinformatics|url={{google books |plainurl=y |id=Uxg51oZNkIsC|page=105}}|date=7 January 2005|publisher=Springer Science & Business Media|isbn=978-0-387-22046-8|pages=105–106}}</ref>

In 2015 [[Nediljko Budisa|N. Budisa]], [[Dieter Söll|D. Söll]] and co-workers reported the full substitution of all 20,899 [[tryptophan]] residues (UGG codons) with unnatural thienopyrrole-alanine in the genetic code of the [[Bacteria|bacterium]] ''[[Escherichia coli|E. coli]]''.<ref>{{cite journal | last1 = Hoesl | first1 = M. G. | last2 = Oehm | first2 = S. | last3 = Durkin | first3 = P. | last4 = Darmon | first4 = E. | last5 = Peil | first5 = L. | last6 = Aerni | first6 = H.-R. | last7 = Rappsilber | first7 = J. | author-link7=Juri Rappsilber | last8 = Rinehart | first8 = J. | last9 = Leach | first9 = D. | last10 = Söll | first10 = D. | last11 = Budisa | first11 = N. | year = 2015 | title = Chemical evolution of a bacterial proteome | journal = Angewandte Chemie International Edition | volume = 54 | issue = 34 | pages = 10030–10034 | doi = 10.1002/anie.201502868 | pmc = 4782924 | pmid=26136259 }} NIHMSID: NIHMS711205</ref>

In 2016 the first stable semisynthetic organism was created. It was a (single cell) bacterium with two synthetic bases (called X and Y). The bases survived cell division.<ref>{{cite web|url=http://www.kurzweilai.net/first-stable-semisynthetic-organism-created|title=First stable semisynthetic organism created {{!}} KurzweilAI|date=3 February 2017|website=www.kurzweilai.net|access-date=2017-02-09}}</ref><ref>{{cite journal | vauthors = Zhang Y, Lamb BM, Feldman AW, Zhou AX, Lavergne T, Li L, Romesberg FE | title = A semisynthetic organism engineered for the stable expansion of the genetic alphabet| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 6 | pages = 1317–1322 | date = February 2017 | pmid = 28115716 | doi = 10.1073/pnas.1616443114 | pmc=5307467| bibcode = 2017PNAS..114.1317Z| doi-access = free}}</ref>

In 2017, researchers in South Korea reported that they had engineered a mouse with an extended genetic code that can produce proteins with unnatural amino acids.<ref>{{cite journal | vauthors = Han S, Yang A, Lee S, Lee HW, Park CB, Park HS | title = Expanding the genetic code of Mus musculus | journal = Nature Communications | volume = 8 | pages = 14568 | date = February 2017 | pmid = 28220771 | doi = 10.1038/ncomms14568 | pmc=5321798| bibcode = 2017NatCo...814568H }}</ref>

In May 2019, researchers reported the creation of a new "Syn61" strain of the ''E. coli'' bacteria. This strain has a fully [[Synthetic biology#Synthetic life|synthetic]] genome that is refactored (all overlaps expanded), recoded (removing the use of three out of 64 codons completely), and further modified to remove the now unnecessary tRNAs and release factors. It is fully [[Genetic viability|viable]] and grows 1.6× slower than its wild-type counterpart "[[Escherichia coli#MDS42|MDS42]]".<ref name="NYT-20190515">{{cite news |last=Zimmer |first=Carl |author-link=Carl Zimmer |title=Scientists Created Bacteria With a Synthetic Genome. Is This Artificial Life? - In a milestone for synthetic biology, colonies of E. coli thrive with DNA constructed from scratch by humans, not nature. |url=https://www.nytimes.com/2019/05/15/science/synthetic-genome-bacteria.html |archive-url=https://ghostarchive.org/archive/20220102/https://www.nytimes.com/2019/05/15/science/synthetic-genome-bacteria.html |archive-date=2022-01-02 |url-access=limited |url-status=live |date=15 May 2019 |work=[[The New York Times]] |access-date=16 May 2019 }}{{cbignore}}</ref><ref name="NAT-20190515">{{cite journal |author=Fredens, Julius |s2cid=205571025 |display-authors=et al. |title=Total synthesis of Escherichia coli with a recoded genome |date=15 May 2019 |journal=[[Nature (journal)|Nature]] |volume=569 |issue=7757 |pages=514–518 |doi=10.1038/s41586-019-1192-5 |pmid=31092918 |pmc=7039709 |bibcode=2019Natur.569..514F }}</ref>