On the enzymatic incorporation of an imidazole nucleotide into DNA

2017 ◽  
Vol 15 (20) ◽  
pp. 4449-4455 ◽  
Author(s):  
Pascal Röthlisberger ◽  
Fabienne Levi-Acobas ◽  
Ivo Sarac ◽  
Philippe Marlière ◽  
Piet Herdewijn ◽  
...  
Keyword(s):  
Genetic Code ◽  
Base Pair ◽  
Nucleoside Triphosphate ◽  
Metal Base ◽  
Modified Nucleoside

We have evaluated the possibility for using an imidazole modified nucleoside triphosphate for the enzymatic construction of artificial metal base pair with view on an expansion of the genetic code.

scholarly journals Enzymatic Formation of an Artificial Base Pair Using a Modified Adenine Nucleoside Triphosphate

2019 ◽  
Author(s):  
Marie Flamme ◽  
Pascal Röthlisberger ◽  
Fabienne Levi-Acobas ◽  
Mohit Chawla ◽  
Romina Oliva ◽  
...  
Keyword(s):  
Base Pair ◽  
In Vitro Selection ◽  
Solid Phase ◽  
Nucleoside Triphosphate ◽  
Dna Duplexes ◽  
Base Pairs ◽  
Metal Base ◽  
Enzymatic Formation ◽  
Genetic Alphabet

The expansion of the genetic alphabet with additional, unnatural base pairs (UBPs) is an important and long standing goal in synthetic biology. Nucleotides acting as ligands for the coordination of metal cations have advanced as promising candidates for such an expansion of the genetic alphabet. However,the inclusion of artificial metal base pairs in nucleic acids mainly relies on solid-phase synthesis approaches and very little is known on polymerase-mediated synthesis. Herein, we report on the selective and high yielding enzymatic construction of a silver-mediated base pair as well as a two-step protocol for the synthesis of DNA duplexes containing a metal UBP. Guided by DFT calculations, we also shed light into the mechanism of formation of this UBP as well as into the structural and energetic preferences. Even though this silver UBP is not directly amenable to in vitro selection experiments, the enzymatic synthesis of this UBP provides valuable insights for the design of future, more potent systems aiming at expanding the genetic alphabet. <br>

Enzymatic Formation of an Artificial Base Pair Using a Modified Adenine Nucleoside Triphosphate

2019 ◽  
Author(s):  
Marie Flamme ◽  
Pascal Röthlisberger ◽  
Fabienne Levi-Acobas ◽  
Mohit Chawla ◽  
Romina Oliva ◽  
...  
Keyword(s):  
Base Pair ◽  
In Vitro Selection ◽  
Solid Phase ◽  
Nucleoside Triphosphate ◽  
Dna Duplexes ◽  
Base Pairs ◽  
Metal Base ◽  
Enzymatic Formation ◽  
Genetic Alphabet

The expansion of the genetic alphabet with additional, unnatural base pairs (UBPs) is an important and long standing goal in synthetic biology. Nucleotides acting as ligands for the coordination of metal cations have advanced as promising candidates for such an expansion of the genetic alphabet. However,the inclusion of artificial metal base pairs in nucleic acids mainly relies on solid-phase synthesis approaches and very little is known on polymerase-mediated synthesis. Herein, we report on the selective and high yielding enzymatic construction of a silver-mediated base pair as well as a two-step protocol for the synthesis of DNA duplexes containing a metal UBP. Guided by DFT calculations, we also shed light into the mechanism of formation of this UBP as well as into the structural and energetic preferences. Even though this silver UBP is not directly amenable to in vitro selection experiments, the enzymatic synthesis of this UBP provides valuable insights for the design of future, more potent systems aiming at expanding the genetic alphabet. <br>

Inhibition of adenovirus DNA polymerase by modified nucleoside triphosphate analogs correlate with their antiviral effects on cellular level

2000 ◽  
Vol 189 (2) ◽  
pp. 91-95 ◽  
Author(s):  
Renate Mentel ◽  
Stefan Kurek ◽  
Ursula Wegner ◽  
Martin v. Janta-Lipinski ◽  
Lutz Gürtler ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Cellular Level ◽  
Nucleoside Triphosphate ◽  
Antiviral Effects ◽  
Modified Nucleoside

scholarly journals A semisynthetic organism engineered for the stable expansion of the genetic alphabet

2017 ◽  
Vol 114 (6) ◽  
pp. 1317-1322 ◽  
Author(s):  
Yorke Zhang ◽  
Brian M. Lamb ◽  
Aaron W. Feldman ◽  
Anne Xiaozhou Zhou ◽  
Thomas Lavergne ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Base Pair ◽  
Genetic Information ◽  
Information Storage ◽  
Nucleoside Triphosphate ◽  
Proof Of Concept ◽  
Sequence Context ◽  
Form Of Life ◽  
Nucleoside Triphosphates ◽  
Genetic Alphabet

All natural organisms store genetic information in a four-letter, two-base-pair genetic alphabet. The expansion of the genetic alphabet with two synthetic unnatural nucleotides that selectively pair to form an unnatural base pair (UBP) would increase the information storage potential of DNA, and semisynthetic organisms (SSOs) that stably harbor this expanded alphabet would thereby have the potential to store and retrieve increased information. Toward this goal, we previously reported thatEscherichia coligrown in the presence of the unnatural nucleoside triphosphates dNaMTP and d5SICSTP, and provided with the means to import them via expression of a plasmid-borne nucleoside triphosphate transporter, replicates DNA containing a single dNaM-d5SICS UBP. Although this represented an important proof-of-concept, the nascent SSO grew poorly and, more problematically, required growth under controlled conditions and even then was unable to indefinitely store the unnatural information, which is clearly a prerequisite for true semisynthetic life. Here, to fortify and vivify the nascent SSO, we engineered the transporter, used a more chemically optimized UBP, and harnessed the power of the bacterial immune response by using Cas9 to eliminate DNA that had lost the UBP. The optimized SSO grows robustly, constitutively imports the unnatural triphosphates, and is able to indefinitely retain multiple UBPs in virtually any sequence context. This SSO is thus a form of life that can stably store genetic information using a six-letter, three-base-pair alphabet.

scholarly journals C-skeleton in the genetic code from a basic series 5 → 0, guiding valences and other numeral features in the code

2021 ◽  
Vol 9 (12) ◽  
Author(s):  
Åsa Wohlin
Keyword(s):  
Amino Acids ◽  
Genetic Code ◽  
Base Pair ◽  
Mean Value ◽  
Atomic Mass ◽  
Side Chain ◽  
Mass Analysis ◽  
Guiding Principle ◽  
Basic Series

The search for regularities in the background for the genetic code and its codon assignments is here further developed, earlier shown to have many correlations with numeral series of integers 5 →0 with different exponents. The atomic mass analysis here counts on 20 + 4 double-coded amino acids, here including Ile AUA as such. A central finding here is that the C-skeleton seems to build on an hierarchical development of the mentioned basic series giving top numbers equal to those returning in side-chain divisions and on first three levels those of C-atoms in base-pair domains. It can very elementary explain the 3/2-division in the weight series. A few main results from earlier articles are shortly recapitulated, since it’s shown here that an x­3-series times 15 (x = integers 5 → 0) joins those earlier aspects and add new ones. It’s found also that atoms with valences 4 + 3 relative those with 2 + 1 make up a 3 to 1-division in both base-pair groups of codon domains, strengthening the earlier observation of valences as one important guiding principle in the relation between codons and domains of amino acids; valences of the atoms which in themselves make up a basic series 5 → 0 in the code when phosphorus P is included. Finally, fundamental factors in the code are gathered, where step 4 →3 seems reign at bottom of the code and number 7, exactly mean value of all atoms.

scholarly journals Enzymatic Formation of an Artificial Base Pair Using a Modified Purine Nucleoside Triphosphate

2020 ◽  
Vol 15 (11) ◽  
pp. 2872-2884
Author(s):  
Marie Flamme ◽  
Pascal Röthlisberger ◽  
Fabienne Levi-Acobas ◽  
Mohit Chawla ◽  
Romina Oliva ◽  
...  
Keyword(s):  
Base Pair ◽  
Purine Nucleoside ◽  
Nucleoside Triphosphate ◽  
Enzymatic Formation

scholarly journals Degeneracy of the genetic code and stability of the base pair at the second position of the anticodon

RNA ◽  
2008 ◽  
Vol 14 (7) ◽  
pp. 1264-1269 ◽  
Author(s):  
J. Lehmann ◽  
A. Libchaber
Keyword(s):  
Genetic Code ◽  
Base Pair

A Two-Unnatural-Base-Pair System toward the Expansion of the Genetic Code

2004 ◽  
Vol 126 (41) ◽  
pp. 13298-13305 ◽  
Author(s):  
Ichiro Hirao ◽  
Yoko Harada ◽  
Michiko Kimoto ◽  
Tsuneo Mitsui ◽  
Tsuyoshi Fujiwara ◽  
...  
Keyword(s):  
Genetic Code ◽  
Base Pair

scholarly journals Genetic code degeneracy is established by the decoding center of the ribosome

2021 ◽  
Author(s):  
Jean Lehmann ◽  
Shixin Ye
Keyword(s):  
Genetic Code ◽  
Base Pair ◽  
Significant Contribution ◽  
Kinetic Scheme ◽  
Evolutionary Models ◽  
Peptidyl Transferase ◽  
Early Appearance ◽  
Evolutionary Step ◽  
The Stability ◽  
Selection Of

The degeneracy of the genetic code confers a wide array of properties to coding sequences. Yet, its origin is still unclear. A structural analysis has shown that the stability of the Watson-Crick base pair at the second position of the anticodon-codon interaction is a critical parameter controlling the extent of non-specific pairings accepted at the third position by the ribosome, a flexibility at the root of degeneracy. Based on recent cryo-EM analyses, the present work shows that residue A1493 of the decoding center provides a significant contribution to the stability of this base pair, revealing that the ribosome is directly involved in the establishment of degeneracy. Building on existing evolutionary models, we show the evidence that the early appearance of A1493 and A1492 established the basis of degeneracy when an elementary kinetic scheme of translation was prevailing. Logical considerations on the expansion of this kinetic scheme indicate that the acquisition of the peptidyl transferase center was the next major evolutionary step, while the induced-fit mechanism, that enables a sharp selection of the tRNAs, necessarily arose later when G530 was acquired by the decoding center.

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