ArticleMicrobial cell factories2015
Optimization of yeast-based production of medicinal protoberberine alkaloids.
Article in Microbial cell factories, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 71 citations in OpenAlex.
- Article
- 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
- Advances in the biosynthesis of naturally occurring benzylisoquinoline alkaloids.Frontiers in plant science · 2025Review
- New insights into the roles of fungi and bacteria in the development of medicinal plant.Journal of advanced research · 2024Review
- De novo production of protoberberine and benzophenanthridine alkaloids through metabolic engineering of yeast.Nature communications · 2024Article
- Review
- A roadmap to establish a comprehensive platform for sustainable manufacturing of natural products in yeast.Nature communications · 2023Review
- Multi-Level Optimization and Strategies in Microbial Biotransformation of Nature Products.Molecules (Basel, Switzerland) · 2023Review
- Development of Biotechnological Photosensitizers for Photodynamic Therapy: Cancer Research and Treatment-From Benchtop to Clinical Practice.Molecules (Basel, Switzerland) · 2022Review
- Plant-microbe hybrid synthesis provides new insights for the efficient use of Macleaya cordata.World journal of microbiology & biotechnology · 2022Article
- Effects of codon optimization, N-terminal truncation and gene dose on the heterologous expression of berberine bridge enzyme.World journal of microbiology & biotechnology · 2022Article
- Catalytic promiscuity ofHorticulture research · 2022Article
- Complete biosynthesis of the bisbenzylisoquinoline alkaloids guattegaumerine and berbamunine in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A computational workflow for the expansion of heterologous biosynthetic pathways to natural product derivatives.Nature communications · 2021Article
- EngineeringaBIOTECH · 2021Review
- Recent Advances in Metabolically Engineered Microorganisms for the Production of Aromatic Chemicals Derived From Aromatic Amino Acids.Frontiers in bioengineering and biotechnology · 2020Review
- Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds.Frontiers in bioengineering and biotechnology · 2020Review
- Complete biosynthesis of noscapine and halogenated alkaloids in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Green Routes for the Production of Enantiopure Benzylisoquinoline Alkaloids.International journal of molecular sciences · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundProtoberberine alkaloids are bioactive molecules abundant in plant preparations for traditional medicines. Yeast engineered to express biosynthetic pathways for fermentative production of these compounds will further enable investigation of the medicinal properties of these molecules and development of alkaloid-based drugs with improved efficacy and safety. Here, we describe the optimization of a biosynthetic pathway in Saccharomyces cerevisiae for conversion of rac-norlaudanosoline to the protoberberine alkaloid (S)-canadine.
resultsThis yeast strain is engineered to express seven heterologous enzymes, resulting in protoberberine alkaloid production from a simple benzylisoquinoline alkaloid precursor. The seven enzymes include three membrane-bound enzymes: the flavin-dependent oxidase berberine bridge enzyme, the cytochrome P450 canadine synthase, and a cytochrome P450 reductase. A number of strategies were implemented to improve flux through the pathway, including enzyme variant screening, genetic copy number variation, and culture optimization, that led to an over 70-fold increase in canadine titer up to 1.8 mg/L. Increased canadine titers enable extension of the pathway to produce berberine, a major constituent of several traditional medicines, for the first time in a microbial host. We also demonstrate that this strain is viable at pilot scale.
conclusionsBy applying metabolic engineering and synthetic biology strategies for increased conversion of simple benzylisoquinoline alkaloids to complex protoberberine alkaloids, this work will facilitate chemoenzymatic synthesis or de novo biosynthesis of these and other high-value compounds using a microbial cell factory.
Indexed as
Identifiers
What OpenQuestion holds
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.