ArticleMetabolic engineering2016
Engineering a microbial platform for de novo biosynthesis of diverse methylxanthines.
Article in Metabolic engineering, 2016. 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, 47 citations in OpenAlex.
- Yeast species resource exploration and application in cell factories.Synthetic and systems biotechnology · 2026Review
- Physicochemical properties, aroma compounds, non-volatile metabolites and their potential correlation inFood chemistry: X · 2025Article
- A green marriage: the union of theophylline's catalytic activity and healing potential.RSC advances · 2025Review
- Computational biology predicts metabolic engineering targets for increased production of 103 valuable chemicals in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Progress in Methylxanthine Biosynthesis: Insights into Pathways and Engineering Strategies.International journal of molecular sciences · 2025Review
- Engineering Saccharomyces cerevisiae for medical applications.Microbial cell factories · 2025Review
- Metabolic modulation and multi-species interaction:Frontiers in cellular and infection microbiology · 2025Article
- POMBOX: A Fission Yeast Cloning Toolkit for Molecular and Synthetic Biology.ACS synthetic biology · 2024Article
- Mixed culture biocatalytic production of the high-value biochemical 7-methylxanthine.Journal of biological engineering · 2023Article
- Article
- Biosynthesis and synthetic biology of psychoactive natural products.Chemical Society reviews · 2021Review
- 3-Methylxanthine production through biodegradation of theobromine by Aspergillus sydowii PT-2.BMC microbiology · 2020Article
- Isolation, characterization and application of theophylline-degrading Aspergillus fungi.Microbial cell factories · 2020Article
- Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds.Frontiers in bioengineering and biotechnology · 2020Review
- Bioassay for Determining the Concentrations of Caffeine and Individual Methylxanthines in Complex Samples.Applied and environmental microbiology · 2019Article
- Applications of Yeast Synthetic Biology Geared towards the Production of Biopharmaceuticals.Genes · 2018Review
- Production of Plant Secondary Metabolites: Examples, Tips and Suggestions for Biotechnologists.Genes · 2018Review
- Accelerating the semisynthesis of alkaloid-based drugs through metabolic engineering.Nature chemical biology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Engineered microbial biosynthesis of plant natural products can support manufacturing of complex bioactive molecules and enable discovery of non-naturally occurring derivatives. Purine alkaloids, including caffeine (coffee), theophylline (antiasthma drug), theobromine (chocolate), and other methylxanthines, play a significant role in pharmacology and food chemistry. Here, we engineered the eukaryotic microbial host Saccharomyces cerevisiae for the de novo biosynthesis of methylxanthines. We constructed a xanthine-to-xanthosine conversion pathway in native yeast central metabolism to increase endogenous purine flux for the production of 7-methylxanthine, a key intermediate in caffeine biosynthesis. Yeast strains were further engineered to produce caffeine through expression of several enzymes from the coffee plant. By expressing combinations of different N-methyltransferases, we were able to demonstrate re-direction of flux to an alternate pathway and develop strains that support the production of diverse methylxanthines. We achieved production of 270μg/L, 61μg/L, and 3700μg/L of caffeine, theophylline, and 3-methylxanthine, respectively, in 0.3-L bench-scale batch fermentations. The constructed strains provide an early platform for de novo production of methylxanthines and with further development will advance the discovery and synthesis of xanthine derivatives.
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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.