ArticlePLoS genetics2013
Directed evolution of a model primordial enzyme provides insights into the development of the genetic code.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- Beyond Protein Building Blocks: A Review of Biological Roles and Therapeutic Potential of Free Amino Acids.International journal of molecular sciences · 2025Review
- Why we are made of proteins and nucleic acids: Structural biology views on extraterrestrial life.Biophysics and physicobiology · 2023Article
- On the Evolutionary History of the Twenty Encoded Amino Acids.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Review
- Transfer RNAs: diversity in form and function.RNA biology · 2021Review
- Article
- Reconstruction and Characterization of Thermally Stable and Catalytically Active Proteins Comprising an Alphabet of ~ 13 Amino Acids.Journal of molecular evolution · 2020Article
- The Future of Origin of Life Research: Bridging Decades-Old Divisions.Life (Basel, Switzerland) · 2020Article
- Engineering microbial pathways for production of bio-based chemicals from lignocellulosic sugars: current status and perspectives.Biotechnology for biofuels · 2020Review
- A tRNA- and Anticodon-Centric View of the Evolution of Aminoacyl-tRNA Synthetases, tRNAomes, and the Genetic Code.Life (Basel, Switzerland) · 2019Review
- Comprehensive reduction of amino acid set in a protein suggests the importance of prebiotic amino acids for stable proteins.Scientific reports · 2018Article
- Directed Chemical Evolution with an Outsized Genetic Code.PloS one · 2016Article
- Methods for the directed evolution of proteins.Nature reviews. Genetics · 2015Review
- In vivo continuous directed evolution.Current opinion in chemical biology · 2015Review
- Experimental evolution of a green fluorescent protein composed of 19 unique amino acids without tryptophan.Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life · 2014Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The contemporary proteinogenic repertoire contains 20 amino acids with diverse functional groups and side chain geometries. Primordial proteins, in contrast, were presumably constructed from a subset of these building blocks. Subsequent expansion of the proteinogenic alphabet would have enhanced their capabilities, fostering the metabolic prowess and organismal fitness of early living systems. While the addition of amino acids bearing innovative functional groups directly enhances the chemical repertoire of proteomes, the inclusion of chemically redundant monomers is difficult to rationalize. Here, we studied how a simplified chorismate mutase evolves upon expanding its amino acid alphabet from nine to potentially 20 letters. Continuous evolution provided an enhanced enzyme variant that has only two point mutations, both of which extend the alphabet and jointly improve protein stability by >4 kcal/mol and catalytic activity tenfold. The same, seemingly innocuous substitutions (Ile→Thr, Leu→Val) occurred in several independent evolutionary trajectories. The increase in fitness they confer indicates that building blocks with very similar side chain structures are highly beneficial for fine-tuning protein structure and function.
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