ArticleMicrobial cell factories2012
De novo production of the flavonoid naringenin in engineered Saccharomyces cerevisiae.
Article in Microbial cell factories, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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115 citing papers in PubMed, 365 citations in OpenAlex.
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- De novo biosynthesis of anthocyanins in Saccharomyces cerevisiae using metabolic pathway synthases from blueberry.Microbial cell factories · 2024Article
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- Advances in Flavonoid Research: Sources, Biological Activities, and Developmental Prospectives.Current issues in molecular biology · 2024Review
- Enhancing (2S)-naringenin production in Saccharomyces cerevisiae by high-throughput screening method based on ARTP mutagenesis.3 Biotech · 2024Article
- Combinatorial optimization of pathway, process and media for the production of p-coumaric acid by Saccharomyces cerevisiae.Microbial biotechnology · 2024Article
- Use of 3-Deoxy-D-arabino-heptulosonic acid 7-phosphate Synthase (DAHP Synthase) to Enhance the Heterologous Biosynthesis of Diosmetin and Chrysoeriol in an Engineered Strain ofInternational journal of molecular sciences · 2024Article
- Systems Metabolic Engineering ofJournal of fungi (Basel, Switzerland) · 2024Article
- Coupling High-Throughput and Targeted Screening for Identification of Nonobvious Metabolic Engineering Targets.ACS synthetic biology · 2024Article
- Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFlavonoids comprise a large family of secondary plant metabolic intermediates that exhibit a wide variety of antioxidant and human health-related properties. Plant production of flavonoids is limited by the low productivity and the complexity of the recovered flavonoids. Thus to overcome these limitations, metabolic engineering of specific pathway in microbial systems have been envisaged to produce high quantity of a single molecules.
resultSaccharomyces cerevisiae was engineered to produce the key intermediate flavonoid, naringenin, solely from glucose. For this, specific naringenin biosynthesis genes from Arabidopsis thaliana were selected by comparative expression profiling and introduced in S. cerevisiae. The sole expression of these A. thaliana genes yielded low extracellular naringenin concentrations (<5.5 μM). To optimize naringenin titers, a yeast chassis strain was developed. Synthesis of aromatic amino acids was deregulated by alleviating feedback inhibition of 3-deoxy-d-arabinose-heptulosonate-7-phosphate synthase (Aro3, Aro4) and byproduct formation was reduced by eliminating phenylpyruvate decarboxylase (Aro10, Pdc5, Pdc6). Together with an increased copy number of the chalcone synthase gene and expression of a heterologous tyrosine ammonia lyase, these modifications resulted in a 40-fold increase of extracellular naringenin titers (to approximately 200 μM) in glucose-grown shake-flask cultures. In aerated, pH controlled batch reactors, extracellular naringenin concentrations of over 400 μM were reached.
conclusionThe results reported in this study demonstrate that S. cerevisiae is capable of de novo production of naringenin by coexpressing the naringenin production genes from A. thaliana and optimization of the flux towards the naringenin pathway. The engineered yeast naringenin production host provides a metabolic chassis for production of a wide range of flavonoids and exploration of their biological functions.
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