Noncanonical Amino Acids in Synthetic Biosafety and Post‐translational Modification Studies

Gang, Donghyeok; Park, Hee-Sung

doi:10.1002/cbic.202000437

Cited by 5 publications

(1 citation statement)

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“…An alternative approach for studying PTMs with the potential of both in vitro and in vivo assays relies on the genetic code expansion technology (Chin, 2014; Liu & Schultz, 2010; Mukai et al, 2017), which is based on the natural protein translation machinery and allows genetic and site‐specific incorporation of unnatural amino acids (UAAs) bearing PTMs or their mimics into proteins during translation (Chen et al, 2018; Gang & Park, 2021). Typically, the genetic code expansion system requires the introduction of an orthogonal aminoacyl‐tRNA synthetase/tRNA pair originally from archaebacteria or Escherichia coli ( E. coli ) into the host cells or organisms together with the gene of interest that carries a premature nonsense codon (e.g., the UAG amber codon) at the target site.…”

Section: Introductionmentioning

confidence: 99%

Functional analysis of protein post‐translational modifications using genetic codon expansion

et al. 2023

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Post-translational modifications (PTMs) of proteins not only exponentially increase the diversity of proteoforms, but also contribute to dynamically modulating the localization, stability, activity, and interaction of proteins. Understanding the biological consequences and functions of specific PTMs has been challenging for many reasons, including the dynamic nature of many PTMs and the technical limitations to access homogenously modified proteins. The genetic code expansion technology has emerged to provide unique approaches for studying PTMs. Through site-specific incorporation of unnatural amino acids (UAAs) bearing PTMs or their mimics into proteins, genetic code expansion allows the generation of homogenous proteins with site-specific modifications and atomic resolution both in vitro and in vivo. With this technology, various PTMs and mimics have been precisely introduced into proteins. In this review, we summarize the UAAs and approaches that have been recently developed to site-specifically install PTMs and their mimics into proteins for functional studies of PTMs.

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Section: Introductionmentioning

confidence: 99%

Functional analysis of protein post‐translational modifications using genetic codon expansion

et al. 2023

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Applications of Genetic Code Expansion in Studying Protein Post-translational Modification

Chen

Tsai

2022

Journal of Molecular Biology

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Cracking the Code: Reprogramming the Genetic Script in Prokaryotes and Eukaryotes to Harness the Power of Noncanonical Amino Acids

Jann,

Giofré,

Bhattacharjee

et al. 2024

Chem. Rev.

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Over 500 natural and synthetic amino acids have been genetically encoded in the last two decades. Incorporating these noncanonical amino acids into proteins enables many powerful applications, ranging from basic research to biotechnology, materials science, and medicine. However, major challenges remain to unleash the full potential of genetic code expansion across disciplines. Here, we provide an overview of diverse genetic code expansion methodologies and systems and their final applications in prokaryotes and eukaryotes, represented by Escherichia coli and mammalian cells as the main workhorse model systems. We highlight the power of how new technologies can be first established in simple and then transferred to more complex systems. For example, whole-genome engineering provides an excellent platform in bacteria for enabling transcript-specific genetic code expansion without off-targets in the transcriptome. In contrast, the complexity of a eukaryotic cell poses challenges that require entirely new approaches, such as striving toward establishing novel base pairs or generating orthogonally translating organelles within living cells. We connect the milestones in expanding the genetic code of living cells for encoding novel chemical functionalities to the most recent scientific discoveries, from optimizing the physicochemical properties of noncanonical amino acids to the technological advancements for their in vivo incorporation. This journey offers a glimpse into the promising developments in the years to come.

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Noncanonical Amino Acids in Synthetic Biosafety and Post‐translational Modification Studies

Cited by 5 publications

References 70 publications

Functional analysis of protein post‐translational modifications using genetic codon expansion

Functional analysis of protein post‐translational modifications using genetic codon expansion

Applications of Genetic Code Expansion in Studying Protein Post-translational Modification

Cracking the Code: Reprogramming the Genetic Script in Prokaryotes and Eukaryotes to Harness the Power of Noncanonical Amino Acids

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