ArticleScientific reports2017
Engineering Saccharomyces cerevisiae for geranylgeraniol overproduction by combinatorial design.
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 18 papers.
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18 citing papers in PubMed.
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- Metabolic engineering of Saccharomyces cerevisiae for enhanced taxadiene production.Microbial cell factories · 2024Article
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- Combinatorial optimization of pathway, process and media for the production of p-coumaric acid by Saccharomyces cerevisiae.Microbial biotechnology · 2024Article
- Improved production of TaxolMicrobial cell factories · 2023Article
- Elimination of enzymes catalysis compartmentalization enhancing taxadiene production inFrontiers in bioengineering and biotechnology · 2023Article
- Isopropanol biosynthesis from crude glycerol using fatty acid precursors via engineered oleaginous yeast Yarrowia lipolytica.Microbial cell factories · 2022Article
- Potential of the Compounds fromMolecules (Basel, Switzerland) · 2022Article
- Carotenoid Biosynthesis: Genome-Wide Profiling, Pathway Identification inFrontiers in nutrition · 2022Article
- Metabolic Engineering ofFrontiers in bioengineering and biotechnology · 2022Article
- Systematic mining of fungal chimeric terpene synthases using an efficient precursor-providing yeast chassis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Enhanced production of taxadiene in Saccharomyces cerevisiae.Microbial cell factories · 2020Article
- Crocetin Overproduction in EngineeredFrontiers in bioengineering and biotechnology · 2020Article
- Dynamic Control ofFrontiers in bioengineering and biotechnology · 2018Article
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7 authors.
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Abstract
Combinatorial design is an effective strategy to acquire the optimal solution in complex systems. In this study, the combined effects of pathway combination, promoters' strength fine-tuning, copy numbers and integration locus variations caused by δ-integration were explored in Saccharomyces cerevisiae using geranylgeraniol (GGOH) production as an example. Two GGOH biosynthetic pathway branches were constructed. In branch 1, GGOH was converted from isopentenyl pyrophosphate (IPP) and farnesyl diphosphate (FPP). In branch 2, GGOH was derived directly from IPP and dimethylallyl pyrophosphate (DMAPP). Regulated by 10 combinations of 11 diverse promoters, a fusion gene BTS1-ERG20, a heterologous geranylgeranyl diphosphate synthase from Sulfolobus acidocaldarius (GGPPSsa) and an endogenous N-terminal truncated gene 3-hydroxyl-3-methylglutaryl-CoA reductase isoenzyme 1 (tHMGR), were incorporated into yeast by δ-integration, leading to a series of GGOH producing strains with yields ranging from 18.45 mg/L to 161.82 mg/L. The yield was further increased to 437.52 mg/L by optimizing the fermentation medium. Consequently, the GGOH yield reached 1315.44 mg/L in a 5-L fermenter under carbon restriction strategy. Our study not only opens large opportunities for downstream diterpenes overproductions, but also demonstrates that pathway optimization based on combinatorial design is a promising strategy to engineer microbes for overproducing natural products with complex structure.
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