- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Genomics and Phylogenetic Studies
- Bacteriophages and microbial interactions
- Chemical Synthesis and Analysis
- RNA modifications and cancer
- DNA and Biological Computing
- Insect and Pesticide Research
- Evolution and Genetic Dynamics
- Synthesis and Reactions of Organic Compounds
- Mosquito-borne diseases and control
- Mechanisms of cancer metastasis
- Bacterial Genetics and Biotechnology
- MXene and MAX Phase Materials
- Click Chemistry and Applications
- Viral Infections and Vectors
Firebird Biomolecular Sciences (United States)
2014-2024
Foundation for Applied Molecular Evolution
2010-2023
Expanding the genetic code DNA and RNA are naturally composed of four nucleotide bases that form hydrogen bonds in order to pair. Hoshika et al. added an additional synthetic nucleotides produce eight-letter generate so-called hachimoji DNA. Coupled with engineered T7 polymerase, this expanded alphabet could be transcribed into RNA. Thus, new forms add information density biopolymers can generated may useful for future biological applications. Science , issue p. 884
Axiomatically, the density of information stored in DNA, with just four nucleotides (GACT), is higher than a binary code, but less it might be if synthetic biologists succeed adding independently replicating to genetic systems. Such addition could also add functional groups not found natural useful for molecular performance. Here, we consider two new (Z and P, 6-amino-5-nitro-3-(1'-β-D-2'-deoxyribo-furanosyl)-2(1H)-pyridone...
Expanding the synthetic biology of artificially expanded genetic information systems (AEGIS) requires tools to make and analyze RNA molecules having added nucleotide "letters". We report here development T7 polymerase reverse transcriptase catalyze transcription xNA (DNA or RNA) two complementary AEGIS nucleobases, 6-amino-5-nitropyridin-2-one (trivially, Z) 2-aminoimidazo[1,2a]-1,3,5-triazin-4(8H)-one P). also MALDI mass spectrometry HPLC-based analyses for oligomeric GACUZP six-letter use...
Abstract The 4-letter DNA alphabet (A, T, G, C) as found in Nature is an elegant, yet non-exhaustive solution to the problem of storage, transfer, and evolution biological information. Here, we report on strategies for both writing reading with expanded alphabets composed up 12 letters C, B, S, P, Z, X, K, J, V). For writing, devise enzymatic strategy inserting a singular, orthogonal xenonucleic acid (XNA) base pair into standard sequences using 2′-deoxy-xenonucleoside triphosphates...
Nucleoside triphosphates having a 3′-ONH2 blocking group have been prepared with and without fluorescent tags on their nucleobases. DNA polymerases were identified that accepted these, adding single nucleotide to the 3′-end of primer in template-directed extension reaction then stops. Nitrite chemistry was developed cleave under mild conditions allow continued extension. Extension-cleavage-extension cycles solution demonstrated untagged nucleotides mixtures tagged nucleotides. Multiple...
Abstract With just four building blocks, low sequence information density, few functional groups, poor control over folding, and difficulties in forming compact folds, natural DNA RNA have been disappointing platforms from which to evolve receptors, ligands, catalysts. Accordingly, synthetic biology has created “artificially expanded genetic systems” (AEGIS) add nucleotides, functionality, density. the expected improvements seen AegisBodies AegisZymes, task for biologists shifts developing...
Synthetic nucleobases presenting non-Watson–Crick arrangements of hydrogen bond donor and acceptor groups can form additional nucleotide pairs that stabilize duplex DNA independent the standard A:T G:C pairs. The pair between 2-amino-3-nitropyridin-6-one 2′-deoxyriboside (presenting a {donor–donor–acceptor} bonding pattern on Watson–Crick face small component, trivially designated Z) imidazo[1,2-a]-1,3,5-triazin-4(8H)one an {acceptor–acceptor–donor} large P) is one these extra for which...
Abstract As one of its goals, synthetic biology seeks to increase the number building blocks in nucleic acids. While efforts towards this goal are well advanced for DNA, they have hardly begun RNA. Herein, we present a crystal structure an RNA riboswitch where stem C:G pair has been replaced by between two components artificially expanded genetic‐information system (AEGIS), Z and P , (6‐amino‐5‐nitro‐2(1 H )‐pyridone 2‐amino‐imidazo[1,2‐a]‐1,3,5‐triazin‐4‐(8 )‐one). The shows that : does not...
One frontier in synthetic biology seeks to move artificially expanded genetic information systems (AEGIS) into natural living cells and arrange the metabolism of those allow them replicate plasmids built from these unnatural systems. In addition requiring polymerases that AEGIS oligonucleotides, such require metabolic pathways biosynthesize triphosphates nucleosides, substrates for polymerases. Such generally nucleoside nucleotide kinases phosphorylate nucleosides nucleotides on path...
In addition to completing the Watson-Crick nucleobase matching "concept" (big pairs with small, hydrogen bond donors pair acceptors), artificially expanded genetic information systems (AEGIS) also challenge DNA polymerases a complete set of mismatches, including wobble mismatches. Here, we explore mismatches AEGIS polymerase 1 from Escherichia coli. Remarkably, find that tolerates an AEGIS:standard has same geometry as G:T have evolved exclude but excludes never encountered in natural...
2,4-Diaminopyrimidine (trivially K) and imidazo[1,2-a]-1,3,5-triazine-2(8H)-4(3H)-dione X) form a nucleobase pair with Watson-Crick geometry as part of an artificially expanded genetic information system (AEGIS). Neither K nor X can any natural nucleobase. Further, neither has accessible tautomeric or protonated/deprotonated state that In vitro experiments show how DNA polymerase I from E. coli manages replication templates one K:X pair, but fails containing two adjacent pairs. analogous in...
One horizon in synthetic biology seeks alternative forms of DNA that store, transcribe, and support the evolution biological information. Here, hydrogen bond donor acceptor groups are rearranged within a Watson–Crick geometry to get 12 nucleotides form 6 independently replicating pairs. Such artificially expanded genetic information systems (AEGIS) Darwinian vitro. To move AEGIS into living cells, metabolic pathways next required make triphosphates economically from their nucleosides,...
Deoxynucleoside kinase from D. melanogaster (DmdNK) has broad specificity; although it catalyzes the phosphorylation of natural pyrimidine more efficiently than purine nucleosides, accepts all four 2′-deoxynucleosides and many analogues, using ATP as a phosphate donor to give corresponding deoxynucleoside monophosphates. Here, we show that replacing single amino acid (glutamine 81 by glutamate) in DmdNK creates variant also nucleosides form part an artificially expanded genetic information...
Abstract As one of its goals, synthetic biology seeks to increase the number building blocks in nucleic acids. While efforts towards this goal are well advanced for DNA, they have hardly begun RNA. Herein, we present a crystal structure an RNA riboswitch where stem C:G pair has been replaced by between two components artificially expanded genetic‐information system (AEGIS), Z and P , (6‐amino‐5‐nitro‐2(1 H )‐pyridone 2‐amino‐imidazo[1,2‐a]‐1,3,5‐triazin‐4‐(8 )‐one). The shows that : does not...
Mit zusätzlichen Nucleotid-„Buchstaben“ ausgestattete Nucleinsäuren lassen sich in funktioneller Weise RNA einbauen. In der Zuschrift auf S. 9991 ff. präsentieren die Gruppen um Piccirilli und Benner erste Molekülstruktur (durch „Fotos“ im Bild symbolisiert) eines funktionalen RNA-Moleküls Basis Sechs-Nucleotid-Alphabets (G, A, U, C sowie künstlichen Nucleotide Z P).
Many efforts have sought to apply laboratory