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( FredensJ., WangK., de la TorreD., FunkeL.F., RobertsonW.E., ChristovaY., ChiaT., SchmiedW.H., DunkelmannD.L., BeránekV. et al (2019) Total synthesis of Escherichia coli with a recoded genome. Nature, 569, 514–518.31092918)
FredensJ., WangK., de la TorreD., FunkeL.F., RobertsonW.E., ChristovaY., ChiaT., SchmiedW.H., DunkelmannD.L., BeránekV. et al (2019) Total synthesis of Escherichia coli with a recoded genome. Nature, 569, 514–518.31092918FredensJ., WangK., de la TorreD., FunkeL.F., RobertsonW.E., ChristovaY., ChiaT., SchmiedW.H., DunkelmannD.L., BeránekV. et al (2019) Total synthesis of Escherichia coli with a recoded genome. Nature, 569, 514–518.31092918, FredensJ., WangK., de la TorreD., FunkeL.F., RobertsonW.E., ChristovaY., ChiaT., SchmiedW.H., DunkelmannD.L., BeránekV. et al (2019) Total synthesis of Escherichia coli with a recoded genome. Nature, 569, 514–518.31092918
( WangK., FredensJ., BrunnerS.F., KimS.H., ChiaT., ChinJ.W. (2016) Defining synonymous codon compression schemes by genome recoding. Nature, 539, 59–64.27776354)
WangK., FredensJ., BrunnerS.F., KimS.H., ChiaT., ChinJ.W. (2016) Defining synonymous codon compression schemes by genome recoding. Nature, 539, 59–64.27776354WangK., FredensJ., BrunnerS.F., KimS.H., ChiaT., ChinJ.W. (2016) Defining synonymous codon compression schemes by genome recoding. Nature, 539, 59–64.27776354, WangK., FredensJ., BrunnerS.F., KimS.H., ChiaT., ChinJ.W. (2016) Defining synonymous codon compression schemes by genome recoding. Nature, 539, 59–64.27776354
M. Lajoie, A. Rovner, Daniel Goodman, Hans Aerni, A. Haimovich, Gleb Kuznetsov, Jaron Mercer, Harris Wang, P. Carr, Joshua Mosberg, N. Rohland, P. Schultz, J. Jacobson, J. Rinehart, G. Church, Farren Isaacs (2013)
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Advance Access Publication Date
( LajoieM.J., RovnerA.J., GoodmanD.B., AerniH.-R.R., HaimovichA.D., KuznetsovG., MercerJ.A., WangH.H., CarrP.A., MosbergJ.A. et al (2013) Genomically recoded organisms expand biological functions. Science, 342, 357–360.24136966)
LajoieM.J., RovnerA.J., GoodmanD.B., AerniH.-R.R., HaimovichA.D., KuznetsovG., MercerJ.A., WangH.H., CarrP.A., MosbergJ.A. et al (2013) Genomically recoded organisms expand biological functions. Science, 342, 357–360.24136966LajoieM.J., RovnerA.J., GoodmanD.B., AerniH.-R.R., HaimovichA.D., KuznetsovG., MercerJ.A., WangH.H., CarrP.A., MosbergJ.A. et al (2013) Genomically recoded organisms expand biological functions. Science, 342, 357–360.24136966, LajoieM.J., RovnerA.J., GoodmanD.B., AerniH.-R.R., HaimovichA.D., KuznetsovG., MercerJ.A., WangH.H., CarrP.A., MosbergJ.A. et al (2013) Genomically recoded organisms expand biological functions. Science, 342, 357–360.24136966
( ChinJ.W. (2017) Expanding and reprogramming the genetic code. Nature, 550, 53–60.28980641)
ChinJ.W. (2017) Expanding and reprogramming the genetic code. Nature, 550, 53–60.28980641ChinJ.W. (2017) Expanding and reprogramming the genetic code. Nature, 550, 53–60.28980641, ChinJ.W. (2017) Expanding and reprogramming the genetic code. Nature, 550, 53–60.28980641
Julius Fredens, Kaihang Wang, D. Torre, Louise Funke, Wesley Robertson, Y. Christova, Tiongsun Chia, W. Schmied, Daniel Dunkelmann, V. Beránek, C. Uttamapinant, A. Llamazares, Thomas Elliott, J. Chin (2019)
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the original work is properly cited.
Kaihang Wang, Julius Fredens, Simon Brunner, Samuel Kim, Tiongsun Chia, J. Chin (2016)
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Synthetic Biology News
( GibsonD.G., GlassJ.I., LartigueC., NoskovV.N., ChuangR.-Y.Y., AlgireM.A., BendersG.A., MontagueM.G., MaL., MoodieM.M. et al (2010) Creation of a bacterial cell controlled by a chemically synthesized genome. Science, 329, 52–56.20488990)
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J. Chin (2017)
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Downloaded from https://academic.oup.com/synbio/article-abstract/4/1/ysz017/5520958 by Ed 'DeepDyve' Gillespie user on 16 October 2019 Synthetic Biology, 2019, 4(1): ysz017 doi: 10.1093/synbio/ysz017 Advance Access Publication Date: 20 June 2019 Synthetic Biology News Life simplified: recompiling a bacterial genome for synonymous codon compression Researchers in the UK recently reported a strain of Escherichia deletion of a previously essential tRNA. This strain also showed coli with a completely synthetic 4-million-base-pair genome (1). increased viability when expressing tRNAs charged with a non- This achievement sets a new world record in synthetic geno- canonical amino acid (ncAA) that targets one of the removed mics by yielding a genome that is four times larger than the codons. The application of synthetic genomics to the laboratory pioneering synthesis of the 1-million-base-pair Mycoplasma workhorse E. coli represents an important step towards enabling mycoides genome (2). Synthetic genomics is enabling the simpli- a future where synthetic biologists can readily design and write fication of recoded organisms, the previous study minimized tailor-made genomes to generate synthetic organisms with the total number of genes and this new study simplified the user-specified functions. Codon compression leads to decreased way those genes are encoded. infection by bacteriophage, as phage protein synthesis is limited Fredens and co-workers constructed an E. coli strain, dubbed by codon incompatibilities, enabling viral resistance to be pro- Syn61, that utilizes just 61 codons for protein synthesis. Cells grammed into genomes (4). Codon compression and genetic typically use 64 codons including 3 that encode termination of code expansion can also be used as a bio-containment strategy protein translation (stop codons). Eighteen of the 20 amino by addicting essential functions of synthetic organisms to the acids are encoded by 2–6 synonymous codons. Nature leverages presence of ncAAs not found in nature (5). It would be especially these redundant codons to regulate the transfer of information interesting to see, Syn61 re-coded for the programmed produc- from DNA to RNA to protein in a variety of ways (3). The extent tion of non-natural biopolymers via ncAAs (5). to which these degenerate codons are needed for cell fitness is not known. To assess this question systematically, the team performed ‘synonymous codon compression’ on the E. coli ge- References nome, recoding 2 of the 6 codons encoding serine (TCG and 1. Fredens,J., Wang,K., de la Torre,D., Funke,L.F., Robertson,W.E., TCA) and the amber stop codon (TAG) with synonymous Christova,Y., Chia,T., Schmied,W.H., Dunkelmann,D.L., codons. This study recoded an astonishing 18 214 codons, Bera ´ nek,V. et al. (2019) Total synthesis of Escherichia coli with a exceeding past recoding efforts by >50-fold (4). recoded genome. Nature, 569, 514–518. To accomplish this tour de force, the authors used homolo- 2. Gibson,D.G., Glass,J.I., Lartigue,C., Noskov,V.N., Chuang,R.- gous recombination in Saccharomyces cerevisiae to assemble 37 Y.Y., Algire,M.A., Benders,G.A., Montague,M.G., Ma,L., bacterial artificial chromosomes (100 kilobase long) from 409 Moodie,M.M. et al. (2010) Creation of a bacterial cell controlled smaller synthetic DNA (10 kilobase). Using a method called by a chemically synthesized genome. Science, 329, 52–56. ‘replicon excision for enhanced genome engineering through 3. Wang,K., Fredens,J., Brunner,S.F., Kim,S.H., Chia,T. and programmed recombination’, or REXER (3), they iteratively Chin,J.W. (2016) Defining synonymous codon compression replaced segments of the E. coli genome with the synthetic DNA schemes by genome recoding. Nature, 539, 59–64. fragments. REXER uses a double selection strategy that lever- 4. Lajoie,M.J., Rovner,A.J., Goodman,D.B., Aerni,H.-R.R., ages unique pairs of positive and negative selection markers Haimovich,A.D., Kuznetsov,G., Mercer,J.A., Wang,H.H., embedded in both the genome and the synthetic DNA fragment Carr,P.A., Mosberg,J.A. et al. (2013) Genomically recoded organ- and CRISPR/Cas9 DNA excision to increase the efficiency of isms expand biological functions. Science, 342, 357–360. lambda red recombination for large DNA fragments (3). The 5. Chin,J.W. (2017) Expanding and reprogramming the genetic authors first performed REXER in parallel targeting eight differ- code. Nature, 550, 53–60. ent genomic regions to generate a library of partially recoded Joshua T. Atkinson* strains. Then, to assemble the full synthetic genome, they Department of BioSciences, Rice University merged the engineered DNA in their strains using conjugative transfer and recombination. Houston, TX 77098, USA Relative to the parental strain, Syn61 displayed only minor growth defects with slightly elongated cells and enabled the *Corresponding author: E-mail: jta2@rice.edu V C The Author(s) 2019. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Synthetic Biology – Oxford University Press
Published: Jan 1, 2019
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