ArticleNature communications2019
Promiscuous enzymatic activity-aided multiple-pathway network design for metabolic flux rearrangement in hydroxytyrosol biosynthesis.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Systems engineering ofSynthetic and systems biotechnology · 2026Article
- Transaminases engineering and their cascade systems for natural product synthesis.Applied biochemistry and biotechnology · 2026Review
- Identification of 4-hydroxyphenethyl alcohol and 6-hydroxynicotinic acid as novel spoilage biomarkers in refrigerated beef.Food chemistry: X · 2026Article
- Systems metabolic engineering for hydroxytyrosol production inApplied and environmental microbiology · 2026Article
- Engineering non-P450 3-hydroxylase forSynthetic and systems biotechnology · 2025Article
- Active site diversification of a non-canonical amino acid decarboxylase by merging substrate multiplexed screening with computationally guided recombination.Protein science : a publication of the Protein Society · 2025Article
- Mutations in active surface sites of NtGGPPS1 enhance carotenoid biosynthesis and drought resistance in Nicotiana tabacum.BMC plant biology · 2025Article
- novoStoic2.0: An integrated framework for pathway synthesis, thermodynamic evaluation, and enzyme selection.PLoS computational biology · 2025Article
- Multifaceted Biological Properties of Verbascoside/Acteoside: Antimicrobial, Cytotoxic, Anti-Inflammatory, and Immunomodulatory Effects.Antibiotics (Basel, Switzerland) · 2025Review
- Directed evolution of L-DOPA sensing and production enables efficient incorporation of an expanded genetic code into proteins.bioRxiv : the preprint server for biology · 2025Article
- From Biosynthesis to Legislation: A Review of Hydroxytyrosol's Biological Functions and Safety.International journal of molecular sciences · 2025Review
- Development of a Multienzyme Cascade for Salvianolic Acid A Synthesis from l-Tyrosine.ACS omega · 2025Article
- Microbial engineering for monocyclic aromatic compounds production.FEMS microbiology reviews · 2025Review
- Multienzyme cascade for synthesis of hydroxytyrosol via engineered Escherichia coli.Scientific reports · 2025Article
- Article
- Hydroxytyrosol isolation, comparison of synthetic routes and potential biological activities.Food science & nutrition · 2024Review
- Engineering a coenzyme-independent dioxygenase for one-step production of vanillin from ferulic acid.Applied and environmental microbiology · 2024Article
- Enhancing the yield of Xenocoumacin 1 in Xenorhabdus nematophila YL001 by optimizing the fermentation process.Scientific reports · 2024Article
- Biosynthesis and Biotechnological Synthesis of Hydroxytyrosol.Foods (Basel, Switzerland) · 2024Review
- Plant-Derived Caffeic Acid and Its Derivatives: An Overview of Their NMR Data and Biosynthetic Pathways.Molecules (Basel, Switzerland) · 2024Review
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11 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Genetic diversity is a result of evolution, enabling multiple ways for one particular physiological activity. Here, we introduce this strategy into bioengineering. We design two hydroxytyrosol biosynthetic pathways using tyrosine as substrate. We show that the synthetic capacity is significantly improved when two pathways work simultaneously comparing to each individual pathway. Next, we engineer flavin-dependent monooxygenase HpaBC for tyrosol hydroxylase, tyramine hydroxylase, and promiscuous hydroxylase active on both tyrosol and tyramine using directed divergent evolution strategy. Then, the mutant HpaBCs are employed to catalyze two missing steps in the hydroxytyrosol biosynthetic pathways designed above. Our results demonstrate that the promiscuous tyrosol/tyramine hydroxylase can minimize the cell metabolic burden induced by protein overexpression and allow the biosynthetic carbon flow to be divided between two pathways. Thus, the efficiency of the hydroxytyrosol biosynthesis is significantly improved by rearranging the metabolic flux among multiple pathways.
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