ArticleNature communications2020
Developing a highly efficient hydroxytyrosol whole-cell catalyst by de-bottlenecking rate-limiting steps.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 100 citations in OpenAlex.
- Systems engineering ofSynthetic and systems biotechnology · 2026Article
- High-yield production of hydroxytyrosol through metabolic engineering ofSynthetic and systems biotechnology · 2026Article
- Promiscuity-Guided Enzyme Evolution via Substrate Multiplexed Screening.Angewandte Chemie (International ed. in English) · 2026Review
- Benzylisoquinoline Alkaloid Production in Yeast via Norlaudanosoline Improves Titer, Selectivity, and Yield.ACS synthetic biology · 2026Article
- Efficient synthesis of l-DOPA inSynthetic and systems biotechnology · 2026Article
- Engineering and Application of Biosensors for Aromatic Compounds Production inMicroorganisms · 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
- Creating novel metabolic pathways by protein engineering for bioproduction.Trends in biotechnology · 2025Review
- Construction of a Plasmid-FreeMetabolites · 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
- Engineering a GPCR-based yeast biosensor for a highly sensitive melatonin detection from fermented beverages.Scientific reports · 2024Article
- Designing a highly efficient type III polyketide whole-cell catalyst with minimized byproduct formation.Biotechnology for biofuels and bioproducts · 2024Article
- Biosynthesis and Biotechnological Synthesis of Hydroxytyrosol.Foods (Basel, Switzerland) · 2024Review
- Exploring the role of flavin-dependent monooxygenases in the biosynthesis of aromatic compounds.Biotechnology for biofuels and bioproducts · 2024Review
- Engineering and application of LacI mutants with stringent expressions.Microbial biotechnology · 2024Article
- 4-Hydroxyphenylacetate 3-Hydroxylase (4HPA3H): A Vigorous Monooxygenase for VersatileInternational journal of molecular sciences · 2024Review
- Advances in 4-Hydroxyphenylacetate-3-hydroxylase Monooxygenase.Molecules (Basel, Switzerland) · 2023Review
- Divergent directed evolution of a TetR-type repressor towards aromatic molecules.Nucleic acids research · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hydroxytyrosol is an antioxidant free radical scavenger that is biosynthesized from tyrosine. In metabolic engineering efforts, the use of the mouse tyrosine hydroxylase limits its production. Here, we design an efficient whole-cell catalyst of hydroxytyrosol in Escherichia coli by de-bottlenecking two rate-limiting enzymatic steps. First, we replace the mouse tyrosine hydroxylase by an engineered two-component flavin-dependent monooxygenase HpaBC of E. coli through structure-guided modeling and directed evolution. Next, we elucidate the structure of the Corynebacterium glutamicum VanR regulatory protein complexed with its inducer vanillic acid. By switching its induction specificity from vanillic acid to hydroxytyrosol, VanR is engineered into a hydroxytyrosol biosensor. Then, with this biosensor, we use in vivo-directed evolution to optimize the activity of tyramine oxidase (TYO), the second rate-limiting enzyme in hydroxytyrosol biosynthesis. The final strain reaches a 95% conversion rate of tyrosine. This study demonstrates the effectiveness of sequentially de-bottlenecking rate-limiting steps for whole-cell catalyst development.
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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.