ArticleCommunications chemistry2023
De novo biosynthesis of berberine and halogenated benzylisoquinoline alkaloids in Saccharomyces cerevisiae.
Article in Communications chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 42 citations in OpenAlex.
- Synthesis of the Natural Product Berberine.ACS omega · 2026Article
- Liposomal drug delivery for lung cancer therapy: progress, challenges, and future perspectives.Molecular cancer · 2026Review
- Article
- Biosynthesis of benzylisoquinoline alkaloids and its evolution in plants.Plant communications · 2026Review
- AI-driven multiscale virtual plant cell modeling: from molecular mechanisms to tissue functions.Planta · 2026Review
- Recent advances in metabolic engineering for microbial production of L-tyrosine.World journal of microbiology & biotechnology · 2026Review
- A Modular Chemoenzymatic Cascade Simplifies Divergent Synthesis of Natural and Unnatural Benzylisoquinoline Alkaloids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A concise enzyme cascade enables the manufacture of natural and halogenated protoberberine alkaloids.Nature communications · 2025Article
- Engineering Saccharomyces cerevisiae for medical applications.Microbial cell factories · 2025Review
- Review
- Convergent evolution of berberine biosynthesis.Science advances · 2024Article
- Ornamental Barberry Twigs as an Underexploited Source of Berberine-Rich Extracts-Preliminary Research.Current issues in molecular biology · 2024Article
- De novo production of protoberberine and benzophenanthridine alkaloids through metabolic engineering of yeast.Nature communications · 2024Article
- Facile Halogenation of Antimicrobial Peptides As Demonstrated by Producing Bromotryptophan-Labeled Nisin Variants with Enhanced Antimicrobial Activity.Journal of natural products · 2024Article
- Intein-mediated temperature control for complete biosynthesis of sanguinarine and its halogenated derivatives in yeast.Nature communications · 2024Article
- Plant antibacterials: The challenges and opportunities.Heliyon · 2024Review
- Strategies, Achievements, and Potential Challenges of Plant and Microbial Chassis in the Biosynthesis of Plant Secondary Metabolites.Molecules (Basel, Switzerland) · 2024Review
- Recent Applications of Protoberberines as Privileged Starting Materials for the Development of Novel Broad-Spectrum Antiviral Agents: A Concise Review (2017-2023).ACS pharmacology & translational science · 2024Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Berberine is an extensively used pharmaceutical benzylisoquinoline alkaloid (BIA) derived from plants. Microbial manufacturing has emerged as a promising approach to source valuable BIAs. Here, we demonstrated the complete biosynthesis of berberine in Saccharomyces cerevisiae by engineering 19 genes including 12 heterologous genes from plants and bacteria. Overexpressing bottleneck enzymes, fermentation scale-up, and heating treatment after fermentation increased berberine titer by 643-fold to 1.08 mg L-1. This pathway also showed high efficiency to incorporate halogenated tyrosine for the synthesis of unnatural BIA derivatives that have higher therapeutical potentials. We firstly demonstrate the in vivo biosynthesis of 11-fluoro-tetrahydrocolumbamine via nine enzymatic reactions. The efficiency and promiscuity of our pathway also allow for the simultaneous incorporation of two fluorine-substituted tyrosine derivatives to 8, 3'-di-fluoro-coclaurine. This work highlights the potential of yeast as a versatile microbial biosynthetic platform to strengthen current pharmaceutical supply chain and to advance drug 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.