ArticleProtein science : a publication of the Protein Society2015
Divergent evolution of a bifunctional de novo protein.
Article in Protein science : a publication of the Protein Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Crystal structure and activity of a de novo enzyme, ferric enterobactin esterase Syn-F4.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Rescue ofeLife · 2023Article
- De novo proteins from random sequences through in vitro evolution.Current opinion in structural biology · 2021Review
- The ascent of man(made oxidoreductases).Current opinion in structural biology · 2018Review
- Designed for life: biocompatible de novo designed proteins and components.Journal of the Royal Society, Interface · 2018Review
- Hierarchical design of artificial proteins and complexes toward synthetic structural biology.Biophysical reviews · 2018Review
- A de novo enzyme catalyzes a life-sustaining reaction in Escherichia coli.Nature chemical biology · 2018Article
- Protein evolution: Hacking an enzyme.Nature chemical biology · 2018Article
- Flexible Proteins at the Origin of Life.Life (Basel, Switzerland) · 2017Article
- A de novo protein confers copper resistance in Escherichia coli.Protein science : a publication of the Protein Society · 2016Article
- Engineering therapeutic protein disaggregases.Molecular biology of the cell · 2016Review
- De Novo Proteins with Life-Sustaining Functions Are Structurally Dynamic.Journal of molecular biology · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primordial proteins, the evolutionary ancestors of modern sequences, are presumed to have been minimally active and nonspecific. Following eons of selective pressure, these early progenitors evolved into highly active and specific proteins. While evolutionary trajectories from poorly active and multifunctional generalists toward highly active specialists likely occurred many times in evolutionary history, such pathways are difficult to reconstruct in natural systems, where primordial sequences are lost to time. To test the hypothesis that selection for enhanced activity leads to a loss of promiscuity, we evolved a de novo designed bifunctional protein. The parental protein, denoted Syn-IF, was chosen from a library of binary patterned 4-helix bundles. Syn-IF was shown previously to rescue two different auxotrophic strains of E. coli: ΔilvA and Δfes. These two strains contain deletions for proteins with very different biochemical functions; IlvA is involved in isoleucine biosynthesis, while Fes is involved in iron assimilation. In two separate experiments, Syn-IF, was evolved for faster rescue of either ΔilvA or Δfes. Following multiple rounds of mutagenesis, two new proteins were selected, each capable of rescuing the selected function significantly faster than the parental protein. In each case, the evolved protein also lost the ability to rescue the unselected function. In both evolutionary trajectories, the original bifunctional generalist was evolved into a monofunctional specialist with enhanced activity.
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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.