ArticleMetabolic engineering2017
Engineering the biocatalytic selectivity of iridoid production in Saccharomyces cerevisiae.
Article in Metabolic engineering, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- Propellane Alkaloid Biosynthesis and Total Synthesis via Interrupted Reaction Pathways.ACS central science · 2026Article
- Identification and Optimization of Kratom Strictosidine Pathway Enabled by Yeast Multiplex Engineering.bioRxiv : the preprint server for biology · 2026Article
- Enhancing Substrate Preference of Iridoid Synthase via Focused Polarity-Steric Mutagenesis Scanning.Chem & bio engineering · 2024Article
- Article
- Engineered biosynthesis of plant heteroyohimbine and corynantheine alkaloids in Saccharomyces cerevisiae.Journal of industrial microbiology & biotechnology · 2024Article
- Review
- Reconstitution of monoterpene indole alkaloid biosynthesis in genome engineered Nicotiana benthamiana.Communications biology · 2022Article
- Article
- Engineered Production of Strictosidine and Analogues in Yeast.ACS synthetic biology · 2022Article
- Identification and functional characterization of three iridoid synthases in Gardenia jasminoides.Planta · 2022Article
- Cell-Free Total Biosynthesis of Plant Terpene Natural Products using an Orthogonal Cofactor Regeneration System.ACS catalysis · 2021Article
- Biosynthesis and synthetic biology of psychoactive natural products.Chemical Society reviews · 2021Review
- AoiQ Catalyzes Geminal Dichlorination of 1,3-Diketone Natural Products.Journal of the American Chemical Society · 2021Article
- Total Synthesis of (-)-Strictosidine and Interception of Aryne Natural Product Derivatives "Strictosidyne" and "Strictosamidyne".Journal of the American Chemical Society · 2021Article
- Developmental Methylome of the Medicinal PlantInternational journal of molecular sciences · 2020Article
- A yeast platform for high-level synthesis of tetrahydroisoquinoline alkaloids.Nature communications · 2020Article
- Production of semi-biosynthetic nepetalactone in yeast.Journal of industrial microbiology & biotechnology · 2019Article
- Engineered mitochondrial production of monoterpenes in Saccharomyces cerevisiae.Metabolic engineering · 2019Article
- Engineering Plant Secondary Metabolism in Microbial Systems.Plant physiology · 2019Article
- Uncoupled activation and cyclization in catmint reductive terpenoid biosynthesis.Nature chemical biology · 2019Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Monoterpene indole alkaloids (MIAs) represent a structurally diverse, medicinally essential class of plant derived natural products. The universal MIA building block strictosidine was recently produced in the yeast Saccharomyces cerevisiae, setting the stage for optimization of microbial production. However, the irreversible reduction of pathway intermediates by yeast enzymes results in a non-recoverable loss of carbon, which has a strong negative impact on metabolic flux. In this study, we identified and engineered the determinants of biocatalytic selectivity which control flux towards the iridoid scaffold from which all MIAs are derived. Development of a bioconversion based production platform enabled analysis of the metabolic flux and interference around two critical steps in generating the iridoid scaffold: oxidation of 8-hydroxygeraniol to the dialdehyde 8-oxogeranial followed by reductive cyclization to form nepetalactol. In vitro reconstitution of previously uncharacterized shunt pathways enabled the identification of two distinct routes to a reduced shunt product including endogenous 'ene'-reduction and non-productive reduction by iridoid synthase when interfaced with endogenous alcohol dehydrogenases. Deletion of five genes involved in α,β-unsaturated carbonyl metabolism resulted in a 5.2-fold increase in biocatalytic selectivity of the desired iridoid over reduced shunt product. We anticipate that our engineering strategies will play an important role in the development of S. cerevisiae for sustainable production of iridoids and MIAs.
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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.