Alstonia scholaris
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1008869 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25773640_1.fastq.gz | Fastqsanger.gz | |||
| SRR25773640_2.fastq.gz | Fastqsanger.gz | |||
| SRR25773641_1.fastq.gz | Fastqsanger.gz | |||
| SRR25773641_2.fastq.gz | Fastqsanger.gz | |||
| SRR25773642_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
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Project description:Monoterpene indole alkaloids (MIAs) are a diverse family of complex plant secondary metabolites with many medicinal properties, including the essential anti-cancer therapeutics vinblastine and vincristine. As MIAs are difficult to chemically synthesize, the world’s supply chain for vinblastine relies on low-yielding extractions of precursors vindoline and catharanthine from the plant Catharanthus roseus, followed by chemical coupling and reduction to form vinblastine. Here, we demonstrate de novo microbial biosynthesis of vindoline and catharanthine from renewable feedstocks such as simple sugar and amino acids using highly engineered yeast. The study showcases the longest biosynthetic pathway refactored into a microbial cell factory to date, including 29 enzymatic steps from the yeast native metabolite geranyl pyrophosphate to catharanthine and vindoline. We made 44 genetic edits to yeast that include expression of 35 heterologous genes from plants as well as deletions, knock-downs, and overexpression of 10 yeast genes or variants thereof to improve the precursor supply. Finally, we demonstrate one-step in vitro vinblastine production using chemical coupling and reduction of vindoline and catharanthine. Not only is the yeast a scalable platform for production of vinblastine, it is also a platform for production of more than 2,000 different natural and new-to-nature MIAs.
2022-08-21 | PXD025067 | Pride
Project description:Metabolic engineering of yeast for de novo production of kratom monoterpene indole alkaloids
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Project description:Saccharomyces cerevisiae ADE8, Phosphoribosyl-glycinamide transformylase; catalyzes a step in the 'de novo' purine nucleotide biosynthetic pathway [Source:SGD;Acc:S000002816], is differentially expressed in 2 experiment(s);
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Project description:Monoterpene indole alkaloids (MIAs) are a diverse family of complex plant secondary metabolites with many medicinal properties, including the essential anti-cancer therapeutics vinblastine and vincristine. As MIAs are difficult to chemically synthesize, the world’s supply chain for vinblastine relies on low-yielding extractions of precursors vindoline and catharanthine from the plant Catharanthus roseus, followed by chemical coupling and reduction to form vinblastine. Here, we demonstrate de novo microbial biosynthesis of vindoline and catharanthine from renewable feedstocks such as simple sugar and amino acids using highly engineered yeast. The study showcases the longest biosynthetic pathway refactored into a microbial cell factory to date, including 29 enzymatic steps from the yeast native metabolite geranyl pyrophosphate to catharanthine and vindoline. We made 44 genetic edits to yeast that include expression of 35 heterologous genes from plants as well as deletions, knock-downs, and overexpression of 10 yeast genes or variants thereof to improve the precursor supply. Finally, we demonstrate one-step in vitro vinblastine production using chemical coupling and reduction of vindoline and catharanthine. Not only is the yeast a scalable platform for production of vinblastine, it is also a platform for production of more than 2,000 different natural and new-to-nature MIAs.
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