ArticleScientific reports2017
Overcoming the plasticity of plant specialized metabolism for selective diterpene production in yeast.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Engineering of plant-derived P450scc forSynthetic and systems biotechnology · 2026Article
- Secondary Metabolite Plasticity inACS omega · 2025Article
- Unraveling the regulatory dynamics of bidirectional promoters for modulating gene co-expression and metabolic flux in Saccharomyces cerevisiae.Nucleic acids research · 2025Article
- Systematic biotechnological production of isoprenoid analogs with bespoke carbon skeletons.Nature communications · 2025Article
- Engineering Saccharomyces cerevisiae for medical applications.Microbial cell factories · 2025Review
- Complete biosynthesis of QS-21 in engineered yeast.Nature · 2024Article
- Sustainable biosynthesis of valuable diterpenes in microbes.Engineering microbiology · 2023Review
- Applications of cell- and tissue-specific 'omics to improve plant productivity.Emerging topics in life sciences · 2022Review
- Metabolic Engineering ofFrontiers in bioengineering and biotechnology · 2022Article
- Orthogonal monoterpenoid biosynthesis in yeast constructed on an isomeric substrate.Nature communications · 2019Article
- Finding and analysing the minimum set of driver nodes required to control multilayer networks.Scientific reports · 2019Article
- Applications of Yeast Synthetic Biology Geared towards the Production of Biopharmaceuticals.Genes · 2018Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plants synthesize numerous specialized metabolites (also termed natural products) to mediate dynamic interactions with their surroundings. The complexity of plant specialized metabolism is the result of an inherent biosynthetic plasticity rooted in the substrate and product promiscuity of the enzymes involved. The pathway of carnosic acid-related diterpenes in rosemary and sage involves promiscuous cytochrome P450s whose combined activity results in a multitude of structurally related compounds. Some of these minor products, such as pisiferic acid and salviol, have established bioactivity, but their limited availability prevents further evaluation. Reconstructing carnosic acid biosynthesis in yeast achieved significant titers of the main compound but could not specifically yield the minor products. Specific production of pisiferic acid and salviol was achieved by restricting the promiscuity of a key enzyme, CYP76AH24, through a single-residue substitution (F112L). Coupled with additional metabolic engineering interventions, overall improvements of 24 and 14-fold for pisiferic acid and salviol, respectively, were obtained. These results provide an example of how synthetic biology can help navigating the complex landscape of plant natural product biosynthesis to achieve heterologous production of useful minor metabolites. In the context of plant adaptation, these findings also suggest a molecular basis for the rapid evolution of terpene biosynthetic pathways.
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