Polymerization of α‐Hydroxy Acids by Ribosomes

Ohta, Atsushi; Murakami, Hiroshi; Suga, Hiroaki

doi:10.1002/cbic.200800439

Cited by 44 publications

(33 citation statements)

References 51 publications

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“…The PTC is a low-specificity enzyme that has maintained the ability to produce a wide variety of condensation products including peptides, esters, and thioesters (Fahnestock et al 1970;Fahnestock and Rich 1971;Hartman et al 2007;Kang and Suga 2008;Ohta et al 2008;Subtelny Fig. 8 Sophisticated catalysis, including specific transition state stabilization by a serine protease.…”

Section: Making Peptide Bondsmentioning

confidence: 99%

The Ribosome Challenge to the RNA World

2015

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An RNA World that predated the modern world of polypeptide and polynucleotide is one of the most widely accepted models in origin of life research. In this model, the translation system shepherded the RNA World into the extant biology of DNA, RNA, and protein. Here, we examine the RNA World Hypothesis in the context of increasingly detailed information available about the origins, evolution, functions, and mechanisms of the translation system. We conclude that the translation system presents critical challenges to RNA World Hypotheses. Firstly, a timeline of the RNA World is problematic when the ribosome is incorporated. The mechanism of peptidyl transfer of the ribosome appears distinct from evolved enzymes, signaling origins in a chemical rather than biological milieu. Secondly, we have no evidence that the basic biochemical toolset of life is subject to substantive change by Darwinian evolution, as required for the transition from the RNA world to extant biology. Thirdly, we do not see specific evidence for biological takeover of ribozyme function by protein enzymes. Finally, we can find no basis for preservation of the ribosome as ribozyme or the universality of translation, if it were the case that other information transducing ribozymes, such as ribozyme polymerases, were replaced by protein analogs and erased from the phylogenetic record. We suggest that an updated model of the RNA World should address the current state of knowledge of the translation system.

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Section: Making Peptide Bondsmentioning

confidence: 99%

The Ribosome Challenge to the RNA World

2015

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“…Over forty years ago, Fahrenstock and colleagues first demonstrated that the ribosome polymerizes phenyllactic acid in a template-directed manner [23]. More recently, Suga and colleagues synthesized polyesters up to ~10 units long containing up to three different side chains by genetic code reprogramming [24,25]. …”

Section: Repurposing Ribosomesmentioning

confidence: 99%

Repurposing ribosomes for synthetic biology

Liu

Kim

Jewett

2017

Current Opinion in Chemical Biology

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The translation system is the cell’s factory for protein biosynthesis, stitching together hundreds to thousands of smaller units of amino acids into proteins, which are required for the structure, function, and regulation of living systems. The extraordinary synthetic capability of this system, which includes the ribosome and its associated factors required for polymerization, has driven extensive efforts to harness it for societal needs in areas as diverse as energy, materials, and medicine. An example is recombinant protein production that has impacted the lives of patients through the synthesis of biopharmaceuticals such as insulin. In nature, however, only limited sets of monomers are utilized, thereby resulting in limited sets of biopolymers (i.e., proteins). Expanding nature’s repertoire of ribosomal monomers could yield new classes of enzymes, therapeutics, materials, and chemicals with diverse genetically encoded chemistry. Here, we discuss recent progress towards engineering ribosomes both in vivo and in vitro. These fundamental and technical breakthroughs open doors for advanced applications in biotechnology and synthetic biology.

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“…Lysine-like substrates (light green) 49 ; Substrates for ester bond formation in the ribosome (grey) 42,54 ; Peptoids (orange) 44c . npAA with D-stereochemistry 45 (purple); Nmethyl amino acids (yellow) 8,43 ; N-alkylated polycyclics (pink) 44a ; Protected npAA allow incorporation charged of N-alkylated amino acids (green) 44b .…”

Section: Flexible Trna-acylation Ribozymes Flexizymesmentioning

confidence: 99%

Discovering functional, non-proteinogenic amino acid containing, peptides using genetic code reprogramming

Rogers

Suga

2015

Org. Biomol. Chem.

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The protein synthesis machinery of the cell, the ribosome and associated factors, is able to accurately follow the canonical genetic code, that which maps RNA sequence to protein sequence, to assemble functional proteins from the twenty or so proteinogenic amino acids. A number of innovative methods have arisen to take advantage of this accurate, and efficient, machinery to direct the assembly of non-proteinogenic amino acids. We review and compare these routes to 'reprogram the genetic code' including in vitro translation, engineered aminoacyl tRNA synthetases, and RNA 'flexizymes'. These studies show that the ribosome is highly tolerant of unnatural amino acids, with hundreds of unusual substrates of varying structure and chemistries being incorporated into protein chains. We also discuss how these methods have been coupled to selection techniques, such as phage display and mRNA display, opening up an exciting new avenue for the production of proteins and peptides with properties and functions beyond that which is possible using proteins composed entirely of the proteinogenic amino acids.

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Polymerization of α‐Hydroxy Acids by Ribosomes

Cited by 44 publications

References 51 publications

The Ribosome Challenge to the RNA World

The Ribosome Challenge to the RNA World

Repurposing ribosomes for synthetic biology

Discovering functional, non-proteinogenic amino acid containing, peptides using genetic code reprogramming

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