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ABSTRACT:
PROVIDER: PRJNA174448 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Root rot disease poses a devastating threat to Coptis chinensis Franch, a medicinal plant prized for its bioactive alkaloids. To dissect its defense mechanisms, we conducted integrated transcriptomic and metabolomic analyses on resistant (R), early-stage infected (S-ES), and late-stage infected (S-LS) plants. Our findings reveal a disease severity-dependent escalation in flavonoid metabolism. Key metabolites, such as kaempferol and quercetin derivatives, were significantly increased compared to R, paralleled by progressive upregulation of biosynthetic genes (PAL, CHS, CHI, FLS). Strikingly, salicylic acid (SA)-associated metabolites and pathway genes (NPR1, NPR3/NPR4) showed no differential expression across groups, contrasting with typical SA-mediated defenses in other species. This study uncovers flavonoid biosynthesis as the primary defense strategy in C. chinensis during root rot progression, while SA signaling may not be the main defense mechanism. These results provide actionable targets for enhancing disease resistance in medicinal plants through metabolic engineering
2025-03-25 | GSE290673 | GEO
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.
2022-09-09 | PXD024976 | panorama
Project description:This dataset belongs to a set of three RNA-Seq experiments that were carried out to study the regulation of monoterpenoid indole alkaloid production in the medicinal plant Catharanthus roseus. For this dataset, C. roseus hairy roots overexpressing the well-known MIA biosynthesis regulator ORCA3 were analyzed by RNA-Seq. As control, C. roseus hairy roots expressing GUS were used. Each analyzed sample consisted of an independent hairy root line; three hairy root lines per construct were analyzed.
2020-09-07 | E-MTAB-9514 | biostudies-arrayexpress
Project description:Metabolic engineering of yeast for de novo production of kratom monoterpene indole alkaloids
| PRJNA1114704 | ENA
Project description:Monoterpene indole alkaloids (MIAs) are a structurally diverse family of specialized metabolites mainly produced in Gentianales to cope with environmental challenges. Due to their pharmacological properties, the biosynthetic modalities of several MIA types have been elucidated but not that of the yohimbanes. Here, we combine transcriptomics and genome sequencing of Rauvolfia tetraphylla with machine learning to discover the unexpected multiple actors of this natural product's synthesis. We identify a medium chain dehydrogenase/reductase (MDR) that produces a mixture of four diastereomers of yohimbanes including the well-known yohimbine and rauwolscine. In addition to this multifunctional yohimbane synthase (YOS), an MDR synthesizing mainly heteroyohimbanes and the short chain dehydrogenase vitrosamine synthase also display a yohimbane synthase side activity. Lastly, we establish that the combination of geissoschizine synthase with at least three other MDRs also produces a yohimbane mixture thus shedding light on the complex mechanisms evolved for the synthesis of these plant bioactives.
2024-01-26 | PXD046315 | Pride
Project description:Catharanthus roseus produces a variety of indole alkaloids with significant biological activities. The indole alkaloids including catharanthine, vindolinine, ajmalicine and the precursor strictosidine were dramatically induced in the leaves following binary stress. To profile the modification of indole alkaloids in C. roseus seedlings under the binary stress of ultraviolet-B irradiation and dark incubation, gel-free proteomic analysis was carried out to uncover the underlying molecular mechanism.
2015-08-24 | PXD001937 | Pride
Project description:Background: Dendrobium officinale, an endangered Chinese herb, has extensive therapeutic effects and contains bioactive ingredients including a large number of polysaccharides and alkaloids, and minimal flavonoids. Firstly, this study attempts to obtain the protocorm-like bodies of this plant through tissue culture to produce the main secondary metabolites whose distribution in each organelle and protocorm like bodies is analyzed. Then, analysis of the correlation between comparative transcriptome sequence and the metabolite content in different organs enables the discovery of putative genes encoding enzymes involved in the biosynthesis of polysaccharides and alkaloids, and flavonoids. Results: The optimum condition for protocorm-like bodies (PLBs) induction and propagation of D. officinale is established. For protocorm induction, we use the seed as the explant, and the optimum medium formula for PLBs propagation is 1/2 MS + α-NAA 0.5 mg·L-1 +6-BA 1.0 mg·L-1 + 2, 4-D 1.5-2.0 mg·L-1 + potato juice 100 g·L-1. The distribution of polysaccharides, alkaloids and flavonoids in D. officinale organs was clarified. Stems, PLBs and leaves have the highest content of polysaccharides, alkaloids and flavonoids, respectively. PLBs replace organs to produce alkaloids in D. officinale, and naringenin was only produced in stem. Hot water extraction (HWE) method was found outperforming the ultrasound-assisted extraction (UAE) method for polysaccharides from D. officinale. A comparative transcriptome analysis of the protocorm-like bodies and leaves of D. officinale showed genes encoding enzymes involved in polysaccharides, alkaloids and flavonoids biosynthetic pathway were differentially expressed. Putative genes encoding enzymes involved in polysaccharides, alkaloids and flavonoids synthetic pathway were identified. Notably, genes encoding enzymes of strictosidine beta-glucosidase, geissoschizine synthase and vinorine synthase in alkaloids biosynthesis of D. officinale are first reported. Conclusions: Our works, especially the identification of candidate genes encoding enzymes involved in metabolites biosynthesis will help to explore and protect the endangered genetic resources and will also facilitate further analysis of the molecular mechanism of secondary metabolites’ biosynthesis in D. officinale.
2021-04-24 | GSE155403 | GEO
Project description:This dataset belongs to a set of three RNA-Seq experiments that were carried out to study the regulation of monoterpenoid indole alkaloid production in the medicinal plant Catharanthus roseus. For this dataset, C. roseus flower petals were infiltrated with Agrobacterium tumefaciens C58C1 or infiltration buffer as control. For each sample, flower petals from four to five flowers, each from a different individual plant were infiltrated.
2020-09-07 | E-MTAB-9517 | biostudies-arrayexpress