ArticlePloS one2015
Synthesis of Morphinan Alkaloids in Saccharomyces cerevisiae.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 114 citations in OpenAlex.
- Metabolomic Insights into Sexual Multi-Morphism of Sinomenine Accumulation inPlants (Basel, Switzerland) · 2025Article
- Codeine 3-O-demethylase catalyzed biotransformation of morphinan alkaloids in Escherichia coli: site directed mutagenesis of terminal residues improves enzyme expression, stability and biotransformation yield.Journal of biological engineering · 2025Article
- Engineering Saccharomyces cerevisiae for medical applications.Microbial cell factories · 2025Review
- Cloning, heterologous expression, and expression analysis of SinSyn7 gene from Sinomenium acutum.PloS one · 2025Article
- The Untapped Potential of Hairy Root Cultures and Their Multiple Applications.International journal of molecular sciences · 2024Review
- Strategies, Achievements, and Potential Challenges of Plant and Microbial Chassis in the Biosynthesis of Plant Secondary Metabolites.Molecules (Basel, Switzerland) · 2024Review
- Biotechnological Approaches to Optimize the Production of Amaryllidaceae Alkaloids.Biomolecules · 2022Review
- Targeting natural products against SARS-CoV-2.Environmental science and pollution research international · 2022Review
- Biotechnological production of specialty aromatic and aromatic-derivative compounds.World journal of microbiology & biotechnology · 2022Review
- Switzerland's Dependence on a Diamorphine Monopoly.Frontiers in psychiatry · 2022Review
- Structural studies of codeinone reductase reveal novel insights into aldo-keto reductase function in benzylisoquinoline alkaloid biosynthesis.The Journal of biological chemistry · 2021Article
- Diversity in Chemical Structures and Biological Properties of Plant Alkaloids.Molecules (Basel, Switzerland) · 2021Review
- Review
- Dual-Use Quickscan: A Web-Based Tool to Assess the Dual-Use Potential of Life Science Research.Frontiers in bioengineering and biotechnology · 2021Article
- EngineeringaBIOTECH · 2021Review
- Biosynthesis and Biological Activities of Newly Discovered Amaryllidaceae Alkaloids.Molecules (Basel, Switzerland) · 2020Review
- Article
- A yeast platform for high-level synthesis of tetrahydroisoquinoline alkaloids.Nature communications · 2020Article
- Biosynthesis of plant tetrahydroisoquinoline alkaloids through an imine reductase route.Chemical science · 2020Article
- Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds.Frontiers in bioengineering and biotechnology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Morphinan alkaloids are the most powerful narcotic analgesics currently used to treat moderate to severe and chronic pain. The feasibility of morphinan synthesis in recombinant Saccharomyces cerevisiae starting from the precursor (R,S)-norlaudanosoline was investigated. Chiral analysis of the reticuline produced by the expression of opium poppy methyltransferases showed strict enantioselectivity for (S)-reticuline starting from (R,S)-norlaudanosoline. In addition, the P. somniferum enzymes salutaridine synthase (PsSAS), salutaridine reductase (PsSAR) and salutaridinol acetyltransferase (PsSAT) were functionally co-expressed in S. cerevisiae and optimization of the pH conditions allowed for productive spontaneous rearrangement of salutaridinol-7-O-acetate and synthesis of thebaine from (R)-reticuline. Finally, we reconstituted a 7-gene pathway for the production of codeine and morphine from (R)-reticuline. Yeast cell feeding assays using (R)-reticuline, salutaridine or codeine as substrates showed that all enzymes were functionally co-expressed in yeast and that activity of salutaridine reductase and codeine-O-demethylase likely limit flux to morphine synthesis. The results of this study describe a significant advance for the synthesis of morphinans in S. cerevisiae and pave the way for their complete synthesis in recombinant microbes.
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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.