ArticleNature chemical biology2014
Bioretrosynthetic construction of a didanosine biosynthetic pathway.
Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 63 citations in OpenAlex.
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- Characterization of a Purine Nucleoside Phosphorylase From Colwellia sp. WH041 for Multienzyme Synthesis of Nucleoside Analogs.Chembiochem : a European journal of chemical biology · 2026Article
- Computational tools for nonnatural pathway design: Algorithms, applications, and challenges.Biodesign research · 2025Review
- An engineered aldolase enables the biocatalytic synthesis of 2'-functionalized nucleoside analogues.Nature synthesis · 2025Article
- Biophysical Characterization of a Novel Phosphopentomutase from the Hyperthermophilic ArchaeonInternational journal of molecular sciences · 2024Article
- Biosynthesis of Arabinoside from Sucrose and Nucleobase via a Novel Multi-Enzymatic Cascade.Biomolecules · 2024Article
- Engineering Substrate Promiscuity of Nucleoside Phosphorylase Via an Insertions-Deletions Strategy.JACS Au · 2024Article
- Recent Developments and Applications of Biocatalytic and Chemoenzymatic Synthesis for the Generation of Diverse Classes of Drugs.Current pharmaceutical biotechnology · 2024Article
- Biocatalytic Synthesis of Antiviral Nucleosides, Cyclic Dinucleotides, and Oligonucleotide Therapies.JACS Au · 2023Review
- Multistep enzyme cascades as a route towards green and sustainable pharmaceutical syntheses.Nature chemistry · 2022Review
- Industrially Relevant Enzyme Cascades for Drug Synthesis and Their Ecological Assessment.International journal of molecular sciences · 2022Review
- Review on molnupiravir as a promising oral drug for the treatment of COVID-19.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2022Review
- Engineered Ribosyl-1-Kinase Enables Concise Synthesis of Molnupiravir, an Antiviral for COVID-19.ACS central science · 2021Article
- Metabolic engineering of Escherichia coli for de novo production of 3-phenylpropanol via retrobiosynthesis approach.Microbial cell factories · 2021Article
- Bioretrosynthesis of FunctionalizedAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- Repurposing Modular Polyketide Synthases and Non-ribosomal Peptide Synthetases for Novel Chemical Biosynthesis.Frontiers in molecular biosciences · 2020Review
- Structure-based design of nucleoside-derived analogues as sulfotransferase inhibitors.RSC advances · 2019Article
- Genetic platforms for heterologous expression of microbial natural products.Natural product reports · 2019Review
- A Retro-biosynthesis-Based Route to Generate Pinene-Derived Polyesters.Chembiochem : a European journal of chemical biology · 2019Article
- Expanding the boundary of biocatalysis: design and optimization of in vitro tandem catalytic reactions for biochemical production.Critical reviews in biochemistry and molecular biology · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Concatenation of engineered biocatalysts into multistep pathways markedly increases their utility, but the development of generalizable assembly methods remains a major challenge. Herein we evaluate 'bioretrosynthesis', which is an application of the retrograde evolution hypothesis, for biosynthetic pathway construction. To test bioretrosynthesis, we engineered a pathway for synthesis of the antiretroviral nucleoside analog didanosine (2',3'-dideoxyinosine). Applying both directed evolution- and structure-based approaches, we began pathway construction with a retro-extension from an engineered purine nucleoside phosphorylase and evolved 1,5-phosphopentomutase to accept the substrate 2,3-dideoxyribose 5-phosphate with a 700-fold change in substrate selectivity and threefold increased turnover in cell lysate. A subsequent retrograde pathway extension, via ribokinase engineering, resulted in a didanosine pathway with a 9,500-fold change in nucleoside production selectivity and 50-fold increase in didanosine production. Unexpectedly, the result of this bioretrosynthetic step was not a retro-extension from phosphopentomutase but rather the discovery of a fortuitous pathway-shortening bypass via the engineered ribokinase.
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Registered trials
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.