ArticleProceedings of the National Academy of Sciences of the United States of America2012
Enzyme functional evolution through improved catalysis of ancestrally nonpreferred substrates.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51 citing papers in PubMed.
- Evolutionary and Functional Characterization of an Auxin Methyltransferase (Ecology and evolution · 2026Article
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- How enzyme functions evolve: genetic, structural, and kinetic perspectives.Biophysical reviews · 2025Review
- Evolution of plant metabolism: the state-of-the-art.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Applications of ancestral sequence reconstruction for understanding the evolution of plant specialized metabolism.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Evolution and diversification of carboxylesterase-like [4+2] cyclases in aspidosperma and iboga alkaloid biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Mutational Road not Taken: Using Ancestral Sequence Resurrection to Evaluate the Evolution of Plant Enzyme Substrate Preferences.Genome biology and evolution · 2024Article
- An ancient metalloenzyme evolves through metal preference modulation.Nature ecology & evolution · 2023Article
- Crystal structure of a family VIII β-lactamase fold hydrolase reveals the molecular mechanism for its broad substrate scope.The FEBS journal · 2022Article
- Using interdisciplinary, phylogeny-guided approaches to understand the evolution of plant metabolism.Plant molecular biology · 2022Review
- A Collaborative Classroom Investigation of the Evolution of SABATH Methyltransferase Substrate Preference Shifts over 120 My of Flowering Plant History.Molecular biology and evolution · 2022Article
- Ancestral sequence reconstruction as a tool to study the evolution of wood decaying fungi.Frontiers in fungal biology · 2022Review
- Ancestral Sequence Reconstruction for Exploring Alkaloid Evolution.Methods in molecular biology (Clifton, N.J.) · 2022Article
- EHreact: Extended Hasse Diagrams for the Extraction and Scoring of Enzymatic Reaction Templates.Journal of chemical information and modeling · 2021Article
- Reenacting the Birth of a Function: Functional Divergence of HIUases and Transthyretins as Inferred by Evolutionary and Biophysical Studies.Journal of molecular evolution · 2021Article
- Convergent Biochemical Pathways for Xanthine Alkaloid Production in Plants Evolved from Ancestral Enzymes with Different Catalytic Properties.Molecular biology and evolution · 2021Article
- Ancestral sequence reconstruction - An underused approach to understand the evolution of gene function in plants?Computational and structural biotechnology journal · 2021Review
- Genome-wide identification and expression analysis ofPlant signaling & behavior · 2020Article
- Elaboration of the Corticosteroid Synthesis Pathway in Primates through a Multistep Enzyme.Molecular biology and evolution · 2020Article
- Phylotranscriptomics of the Pentapetalae Reveals Frequent Regulatory Variation in Plant Local Responses to the Fungal PathogenThe Plant cell · 2020Article
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9 authors.
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Abstract
In this study, we investigated the role for ancestral functional variation that may be selected upon to generate protein functional shifts using ancestral protein resurrection, statistical tests for positive selection, forward and reverse evolutionary genetics, and enzyme functional assays. Data are presented for three instances of protein functional change in the salicylic acid/benzoic acid/theobromine (SABATH) lineage of plant secondary metabolite-producing enzymes. In each case, we demonstrate that ancestral nonpreferred activities were improved upon in a daughter enzyme after gene duplication, and that these functional shifts were likely coincident with positive selection. Both forward and reverse mutagenesis studies validate the impact of one or a few sites toward increasing activity with ancestrally nonpreferred substrates. In one case, we document the occurrence of an evolutionary reversal of an active site residue that reversed enzyme properties. Furthermore, these studies show that functionally important amino acid replacements result in substrate discrimination as reflected in evolutionary changes in the specificity constant (k(cat)/K(M)) for competing substrates, even though adaptive substitutions may affect K(M) and k(cat) separately. In total, these results indicate that nonpreferred, or even latent, ancestral protein activities may be coopted at later times to become the primary or preferred protein activities.
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