Independent evolution of ipecac alkaloid biosynthesis
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ABSTRACT:
PROVIDER: PRJEB80476 | ENA |
REPOSITORIES: ENA
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Project description:MicroRNAs (miRNA) are ~21 nucleotide long, small endogenous non-coding RNAs that functioning in regulation of gene expression found in many eukaryotes. In this study, small RNA libraries of opium poppy from four different tissues (leaf, root, capsule, stem) were sequenced using high-throughput next generation Illumina sequencing (Solexa) technology to investigate potential mode of actions of miRNAs in alkaloid biosynthesis. A total of 27 opium poppy miRNAs which have roles in regulation of alkaloid biosynthesis were identified in this study.
2014-12-15 | GSE62716 | GEO
Project description:MicroRNAs (miRNA) are ~21 nucleotide long, small endogenous non-coding RNAs that functioning in regulation of gene expression found in many eukaryotes. In this study, small RNA libraries of opium poppy from four different tissues (leaf, root, capsule, stem) were sequenced using high-throughput next generation Illumina sequencing (Solexa) technology to investigate potential mode of actions of miRNAs in alkaloid biosynthesis. A total of 27 opium poppy miRNAs which have roles in regulation of alkaloid biosynthesis were identified in this study. A six chip study using miRNA isolated from four separate tissues (capsule, leaf, stem, root). small RNA libraries of opium poppy tissues were sequenced using high-throughput next generation Illumina sequencing (Solexa) technology to investigate potential mode of actions of miRNAs in alkaloid biosynthesis. Furthermore, the novel opium poppy miRNAs were also confirmed by a direct small RNA cloning strategy. The microarray platform were performed to measure and analyze the mirnome of the different opium poppy tissues.
2014-12-15 | E-GEOD-62716 | biostudies-arrayexpress
Project description: Not available
| S-EPMC7317620 | biostudies-literature
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| S-EPMC10151470 | biostudies-literature
Project description:We analyzed the transcriptome of A. acutangulus roots by deep RNA sequencing to dig TAs biosynthetic genes. KOG (Eukaryotic Orthologous Groups) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses identified 48 unigenes referring to the tropane, piperidine and pyridine alkaloid biosynthesis, 145 unigenes presumably involved in distribution of arginine to TAs biosynthesis, and 86 unigenes referring to the terpenoid backbone biosynthesis. Furthermore, 82 unigenes annotated as cytochrome P450 family members seemed to be involved in secondary metabolism pathways. Previously unknown TAs biosynthetic genes in A. acutangulus, which encode littorine mutase/monooxygenase (CYP80F1) and diamine oxidase (DAO), were identified by this study.
2016-07-08 | GSE62162 | GEO
Project description:Steroidal alkaloids are FDA-approved drugs (e.g., Zytiga) and promising drug candidates/leads (e.g., cyclopamine); yet many of the ≥ 697 known steroidal alkaloid natural products remain underutilized as drugs because it can be challenging to scale their biosynthesis in their producing organisms. Cyclopamine is a steroidal alkaloid produced by corn lily (Veratrum spp.) plants, and it is an inhibitor of the Hedgehog (Hh) signaling pathway. Therefore, cyclopamine is an important drug candidate/lead to treat human diseases that are associated with dysregulated Hh signaling, such as basal cell carcinoma and acute myeloid leukemia. Cyclopamine and its semi-synthetic derivatives have been studied in (pre)clinical trials as Hh inhibitor-based drugs. However, challenges in scaling the production of cyclopamine have slowed efforts to improve its 1 efficacy and safety profile through (bio)synthetic derivatization, often limiting drug development to synthetic analogs of cyclopamine such as the FDA-approved drugs Odomzo, Daurismo, and Erivedge. If a platform for the scalable and sustainable production of cyclopamine were established, then its (bio)synthetic derivatization, clinical development, and, ultimately, widespread distribution could be accelerated. Ongoing efforts to achieve this goal include the biosynthesis of cyclopamine in Veratrum plant cell culture and the semi-/total chemical synthesis of cyclopamine. Herein, this work advances efforts towards a promising future approach: the biosynthesis of cyclopamine in engineered microorganisms. We completed the heterologous microbial production of verazine (biosynthetic precursor to cyclopamine) from simple sugars (i.e., glucose and galactose) in engineered Saccharomyces cerevisiae (S. cerevisiae) through the inducible upregulation of the native yeast mevalonate and lanosterol biosynthetic pathways, diversion of biosynthetic flux from ergosterol (i.e., native sterol in S. cerevisiae) to cholesterol (i.e., biosynthetic precursor to verazine), and expression of a refactored five-step verazine biosynthetic pathway containing eight heterologous enzymes sourced from seven different species. Importantly, S. cerevisiae-produced verazine was indistinguishable via liquid chromatography-mass spectrometry from both a commercial standard (Veratrum spp. plant-produced) and Nicotiana benthamiana-produced verazine. To the best of our knowledge, this is the first report describing the heterologous production of a steroidal alkaloid in an engineered yeast. Verazine production was increased through design-build-test-learn cycles to a final titer of 27 ± 2 μg/L (1.7 ± 0.1 μg/g DCW). Together, this research lays the groundwork for future microbial biosynthesis of cyclopamine, (bio)synthetic derivatives of cyclopamine, and other steroidal alkaloid natural products.
2025-03-08 | PXD053024 | Pride
Project description:Tobacco with modified genetics controlling alkaloid accumulation has been of interest because of the possibility of mandated lowering of nicotine levels in combustible cigarettes by regulatory authorities. Transcription factors coded by the Nic1, Nic2, and Myc2a loci act as positive regulators of genes directly involved in alkaloid accumulation. Different combinations of alternative alleles at these loci were assembled in homozygous nearly isogenic lines (NILs). Recessive nic1/nic2 alleles were found to have greater influence on alkaloid reduction as compared to a mutant myc2a allele. When combined into single genotypes, these alleles operated in an additive manner to further reduce alkaloid levels in field and greenhouse experiments. This was at the expense of reduced cured leaf quality, however. An RNA-seq experiment was carried out to investigate global changes in root expression due to different genotypes at these three loci. Up to 681 differentially expressed genes (DEGs) were identified between the studied NILs, with expression of most DEGs being downregulated by recessive alleles. In general, the mutant myc2a allele appeared to suppress a subset of previously characterized alkaloid biosynthetic genes with relatively weaker effect as compared to the nic1/nic2 alleles. There was little evidence that root expression of Nic1 or Nic2 genes was affected by allelic variability at the Myc2a locus, or vice versa. The list of DEGs influenced by genotypes at these three loci may contain candidate genes coding for currently uncharacterized enzymes involved with tobacco alkaloid accumulation.
2025-05-28 | GSE284841 | GEO
Project description: Not available
| S-EPMC5873419 | biostudies-literature
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| S-EPMC7614287 | biostudies-literature
Project description:Plants produce diverse molecules that inhibit protein translation. A lead example is homoharringtonine (HHT), both a key tool for ribosomal profiling and an FDA-approved treatment for chronic myeloid leukemia. HHT is commercially produced through semi-synthesis by esterifying the alkaloid core cephalotaxine (CET) extracted from endangered Cephalotaxus species. Despite its medicinal significance, a biosynthetic pathway to CET and HHT has not been described. Here, we use paired untargeted metabolomics (stable-isotope labeled precursor feeding) and transcriptomics to elucidate a near-complete biosynthesis to CET without prior knowledge of intermediates and biosynthetic genes. We show that while CET alkaloid core is actively biosynthesized only in growing root tips, both CET and HHT accumulate throughout the plant. We discovered and characterized seven CET pathway intermediates and six novel biosynthetic enzymes that can be used to produce cephalotaxinone, the likely direct precursor of CET. Included are non-canonical cytochrome P450s, an atypical short-chain dehydrogenase, and a 2-oxoglutarate-dependent dioxygenase that together result in carbon excision and pentacyclic backbone formation of HHT alkaloids. This study establishes a metabolic route to the core scaffold of HHT and suggests a whole plant coordination model for biosynthesis of eukaryotic ribosomal toxins in Cephalotaxus, where cephalotaxinone is the last pathway intermediate produced in root tips and distributed throughout the plant for subsequent elaboration to HHT.
2026-02-25 | GSE319274 | GEO