ArticleJournal of the American Chemical Society2019
Optimization of Replication, Transcription, and Translation in a Semi-Synthetic Organism.
Article in Journal of the American Chemical Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 68 citations in OpenAlex.
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- Recognition of unnatural base pairs by a eukaryotic DNA polymerase enables universal sequencing of an expanded genetic alphabet.Nucleic acids research · 2026Article
- Reprogramming the genetic code with flexizymes.Nature reviews. Chemistry · 2024Review
- Assembly of functional microbial ecosystems: from molecular circuits to communities.FEMS microbiology reviews · 2024Review
- Reverse transcription as key step in RNARSC chemical biology · 2024Article
- Investigation of the stability of D5SIC-DNAM-incorporated DNA duplex inPhysical chemistry chemical physics : PCCP · 2024Article
- Investigation of dynamical flexibility of D5SIC-DNAM inside DNA duplex in aqueous solution: a systematic classical MD approach.Physical chemistry chemical physics : PCCP · 2024Article
- Xeno Amino Acids: A Look into Biochemistry as We Do Not Know It.Life (Basel, Switzerland) · 2023Review
- Locating, tracing and sequencing multiple expanded genetic letters in complex DNA context via a bridge-base approach.Nucleic acids research · 2023Article
- Discovery, implications and initial use of semi-synthetic organisms with an expanded genetic alphabet/code.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Structural basis of transcription recognition of a hydrophobic unnatural base pair by T7 RNA polymerase.Nature communications · 2023Article
- From polymerase engineering to semi-synthetic life: artificial expansion of the central dogma.RSC chemical biology · 2022Review
- A Closer Look at Non-random Patterns Within Chemistry Space for a Smaller, Earlier Amino Acid Alphabet.Journal of molecular evolution · 2022Article
- "Click handle"-modified 2'-deoxy-2'-fluoroarabino nucleic acid as a synthetic genetic polymer capable of post-polymerization functionalization.Chemical science · 2022Article
- Genetic Code Engineering by Natural and Unnatural Base Pair Systems for the Site-Specific Incorporation of Non-Standard Amino Acids Into Proteins.Frontiers in molecular biosciences · 2022Review
- Improving the Efficiency and Orthogonality of Genetic Code Expansion.Biodesign research · 2022Review
- Transcriptional processing of an unnatural base pair by eukaryotic RNA polymerase II.Nature chemical biology · 2021Article
- Therapeutic promise of engineered nonsense suppressor tRNAs.Wiley interdisciplinary reviews. RNA · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Previously, we reported the creation of a semi-synthetic organism (SSO) that stores and retrieves increased information by virtue of stably maintaining an unnatural base pair (UBP) in its DNA, transcribing the corresponding unnatural nucleotides into the codons and anticodons of mRNAs and tRNAs, and then using them to produce proteins containing noncanonical amino acids (ncAAs). Here we report a systematic extension of the effort to optimize the SSO by exploring a variety of deoxy- and ribonucleotide analogues. Importantly, this includes the first in vivo structure-activity relationship (SAR) analysis of unnatural ribonucleoside triphosphates. Similarities and differences between how DNA and RNA polymerases recognize the unnatural nucleotides were observed, and remarkably, we found that a wide variety of unnatural ribonucleotides can be efficiently transcribed into RNA and then productively and selectively paired at the ribosome to mediate the synthesis of proteins with ncAAs. The results extend previous studies, demonstrating that nucleotides bearing no significant structural or functional homology to the natural nucleotides can be efficiently and selectively paired during replication, to include each step of the entire process of information storage and retrieval. From a practical perspective, the results identify the most optimal UBP for replication and transcription, as well as the most optimal unnatural ribonucleoside triphosphates for transcription and translation. The optimized SSO is now, for the first time, able to efficiently produce proteins containing multiple, proximal ncAAs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.