Single-cell multi-omics in the medicinal plant Catharanthus roseus

Nature Chemical Biology, Journal Year: 2023, Volume and Issue: 19(8), P. 1031 - 1041

Published: May 15, 2023

Advances in omics technologies now permit the generation of highly contiguous genome assemblies, detection transcripts and metabolites at level single cells high-resolution determination gene regulatory features. Here, using a complementary, multi-omics approach, we interrogated monoterpene indole alkaloid (MIA) biosynthetic pathway Catharanthus roseus, source leading anticancer drugs. We identified clusters genes involved MIA biosynthesis on eight C. roseus chromosomes extensive duplication genes. Clustering was not limited to linear genome, through chromatin interaction data, were present within same topologically associated domain, permitting identification secologanin transporter. Single-cell RNA-sequencing revealed sequential cell-type-specific partitioning leaf that, when coupled with single-cell metabolomics permitted reductase that yields bis-indole anhydrovinblastine. also expression root pathway.

Language: Английский

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Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 20, 2024

Abstract Cepharanthine is a secondary metabolite isolated from Stephania . It has been reported that it anti-conronaviruses activities including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we assemble three genomes ( S. japonica , yunnanensis and cepharantha ), propose the cepharanthine biosynthetic pathway, assess antiviral potential of compounds involved in pathway. Among genomes, near telomere-to-telomere assembly with one remaining gap, have chromosome-level assemblies. Following by gene mining metabolomics analysis, identify seven analogs broad-spectrum anti-coronavirus activities, SARS-CoV-2, Guangxi pangolin-CoV (GX_P2V), swine diarrhoea coronavirus (SADS-CoV), porcine epidemic diarrhea virus (PEDV). We also show two other genera, Nelumbo Thalictrum can produce analogs, thus for compound discovery. Results generated this study could accelerate drug

Language: Английский

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Plant terpenoid biosynthetic network and its multiple layers of regulation

Progress in Lipid Research, Journal Year: 2024, Volume and Issue: 95, P. 101287 - 101287

Published: June 19, 2024

Language: Английский

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The genomes of medicinal skullcaps reveal the polyphyletic origins of clerodane diterpene biosynthesis in the family Lamiaceae

Molecular Plant, Journal Year: 2023, Volume and Issue: 16(3), P. 549 - 570

Published: Jan. 13, 2023

The presence of anticancer clerodane diterpenoids is a chemotaxonomic marker for the traditional Chinese medicinal plant Scutellaria barbata, although molecular mechanisms behind biosynthesis are unknown. Here, we report high-quality assembly 414.98 Mb genome S. barbata into 13 pseudochromosomes. Using phylogenomic and biochemical data, mapped plastidial metabolism kaurene (gibberellins), abietane, diterpenes in three species family Lamiaceae (Scutellaria baicalensis, Salvia splendens), facilitating identification genes involved clerodanes, kolavenol, isokolavenol. We show that evolved through recruitment neofunctionalization from gibberellin abietane metabolism. Despite assumed monophyletic origin biosynthesis, which widespread Lamiaceae, our data distinct evolutionary lineages suggest polyphyletic origins Lamiaceae. Our study not only provides significant insights evolution biosynthetic pathways mint family, but also will facilitate production clerodanes future metabolic engineering efforts.

Language: Английский

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Biosynthesis of the allelopathic alkaloid gramine in barley by a cryptic oxidative rearrangement

Science, Journal Year: 2024, Volume and Issue: 383(6690), P. 1448 - 1454

Published: March 28, 2024

The defensive alkaloid gramine not only protects barley and other grasses from insects but also negatively affects their palatability to ruminants. key gene for formation has remained elusive, hampering breeding initiatives. In this work, we report that a encoding cytochrome P450 monooxygenase CYP76M57, which name AMI synthase (AMIS), enables the production of in

Language: Английский

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Tomato root specialized metabolites evolved through gene duplication and regulatory divergence within a biosynthetic gene cluster

Science Advances, Journal Year: 2024, Volume and Issue: 10(17)

Published: April 24, 2024

Tremendous plant metabolic diversity arises from phylogenetically restricted specialized pathways. Specialized metabolites are synthesized in dedicated cells or tissues, with pathway genes sometimes colocalizing biosynthetic gene clusters (BGCs). However, the mechanisms by which spatial expression patterns arise and role of BGCs evolution remain underappreciated. In this study, we investigated driving acylsugar Solanaceae. Previously thought to be glandular trichomes, acylsugars were recently found cultivated tomato roots. We demonstrated that roots trichomes have different sugar cores, identified root-enriched paralogs trichome genes, characterized a key paralog required for root biosynthesis,

Language: Английский

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Prediction of the reaction mechanisms of sesquiterpene coumarin synthases supports a direct evolutionary link with triterpene biosynthesis

Phytochemistry Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Language: Английский

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Genome sequencing of three Polyscias species reveals common features in terpene synthase gene family evolution in these species

The Plant Genome, Journal Year: 2025, Volume and Issue: 18(1)

Published: Feb. 19, 2025

Abstract The genus Polyscias , part of the Araliaceae family, is known for its significant ornamental and medicinal value, as well rich variety metabolites. These plants are primarily found in tropical regions, particularly Southeast Asia Pacific islands. diverse geographical environments have led to emergence many unique endangered species, although there limited genomic information available about them. In this study, we generated high‐quality reference genomes three species: two that endemic Hawaiʻi, cf. bisattenuata lallanii one more widespread macgillivrayi . We identified a total 51,083, 60,881, 29,060 genes these respectively. Whole‐genome duplication analysis indicated all species underwent common event. By examining phylogenetic structural characteristics terpene synthase gene family closely related several clusters play crucial roles metabolite synthesis. A mono‐ sesquiterpenoids were detected, with compounds having been validated previous studies. Our findings provide foundation further genetic biochemical investigations which may aid conservation species.

Language: Английский

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Toward an integrated omics approach for plant biosynthetic pathway discovery in the age of AI

Trends in Biochemical Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Comprehensive mutant chemotyping reveals embedding of a lineage-specific biosynthetic gene cluster in wider plant metabolism

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(12)

Published: March 19, 2025

Plants produce diverse specialized metabolites with important ecological functions. It has recently become apparent that the genes for many of these pathways are not dispersed in plant genomes, but rather arranged like beads on a string biosynthetic gene clusters (BGCs). Pathways encoded by BGCs as rule dedicated linear do form parts wider metabolic networks. In contrast, biosynthesis widely distributed more ancestral such carotenoids and anthocyanins clustered. Little is known about how evolved clustered interact general metabolism. We characterized 12-gene BGC antimicrobial defense compound avenacin A-1, triterpene glycoside produced oats. Avenacin A-1 acylated fluorophore N -methyl anthranilate confers bright blue fluorescence oat root tips under ultraviolet light. Here, we exploit suite >100 avenacin-deficient mutants identified screening reduced to identify required function this paradigm BGC. Using combination mutant chemotyping, biochemical molecular analysis, genome resequencing, two nonclustered ( Sad4 Pal2 ) encoding enzymes synthesize donors glycosylation acylation (recruited from phenylpropanoid tryptophan pathways). Our finding Cluster Auxiliary Enzymes (CAEs) provides insights into interplay between metabolism newly lineage-specific

Language: Английский

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