Exogenous stimulation of Tanacetum vulgare roots with pipecolic acid leads to tissue-specific responses in terpenoid composition.

Tanacetum vulgare L., tansy, is a perennial plant with highly variable terpenoid composition, with mono- and sesquiterpenoids being the most abundant. The high diversity of terpenoids plays an important role in mediating ecological interactions. However, the distribution of terpenoids in different tissues and inducibility of terpenoids in these tissues via biotic stress are poorly understood. We investigated changes in terpenoid profiles and concentrations in different organs following treatment of roots with pipecolic acid (Pip), a non-proteinogenic amino acid that triggers defence responses leading to induce systemic resistance (SAR) in plants. Tansy leaves and midribs contained mainly monoterpenoids, while coarse and fine roots contained mainly sesquiterpenoids. Rhizomes contained terpenoid profiles of both midribs and roots but also unique compounds. Treatment with Pip led to an increase in concentrations of mono- and sesquiterpenoids in all tissues except rhizomes. However, significantly more sesquiterpenoids was formed in root tissues in response to Pip treatment, compared to shoots. The metabolic atlas for terpenoids presented here shows that there is exceptionally strong differentiation of terpenoid patterns and terpenoid content in different tissues of tansy. This, together with differential inducibility by Pip, suggests that the chemical diversity of terpenoids may play an important role in tansy ecological interactions and defence against biotic stressors that feed on below- and aboveground organs.

Efficient clustering of large molecular libraries.

The widespread use of Machine Learning (ML) techniques in chemical applications has come with the pressing need to analyze extremely large molecular libraries. In particular, clustering remains one of the most common tools to dissect the chemical space. Unfortunately, most current approaches present unfavorable time and memory scaling, which makes them unsuitable to handle million- and billion-sized sets. Here, we propose to bypass these problems with a time- and memory-efficient clustering algorithm, BitBIRCH. This method uses a tree structure similar to the one found in the Balanced Iterative Reducing and Clustering using Hierarchies (BIRCH) algorithm to ensure O N time scaling. BitBIRCH leverages the instant similarity (iSIM) formalism to process binary fingerprints, allowing the use of Tanimoto similarity, and reducing memory requirements. Our tests show that BitBIRCH is already > 1,000 times faster than standard implementations of the Taylor-Butina clustering for libraries with 1,500,000 molecules. BitBIRCH increases efficiency without compromising the quality of the resulting clusters. We explore strategies to handle large sets, which we applied in the clustering of one billion molecules under 5 hours using a parallel/iterative BitBIRCH approximation.

The Secondary Metabolites from Genus Kitasatospora: A Promising Source for Drug Discovery.

Microbial secondary metabolites are well-known resource for drug discovery. Kitasatospora is one of the rare genera of Actinomycetes and important antibiotics producer that are not fully explored. Recently an explosively increasing number of reports have proved that the genus is capable of producing various bioactive secondary metabolites. Here, we comprehensively summarized secondary metabolites from Kitasatospora strains including their chemical structures, biological effects, mechanisms of actions together with the related genomic and biosynthetic analyses. The review covered more than 100 metabolites with their significant pharmacological properties which included a class of peptide aldehyde natural products that had been optimized to a promising lead compound. This work provides detailed information of Kitasatospora-derived natural products and presents their potential for therapeutically relevant utilization, which would inspire the drug discovery from this genus in future.

A Novel C3/C4-Fused Indole Scaffold through Acid-Catalyzed Cascade Reaction.

3,4-bridged indoles are underrepresented among the vast number of indoles described in the literature. Attempts to access 3,4-macrocyclized indoles led to the unexpected formation of a novel tetracyclic indole through intramolecular acid-catalyzed ring contraction. The herein-established one-step synthetic route provides an excellent medicinal chemistry platform for the construction of screening libraries covering a unique chemical space of indoles.

Chemical Diversity, Pharmacology, Synthesis and Detection of Naturally Occurring Peroxides.

Natural occurring peroxides are interesting bioprospecting targets due to their molecular structural diversity and the wide range of pharmacological activities. In this systematic review, a total of 123 peroxide compounds were analysed from 99 published papers with the compounds distributed in 31 plants, 18 animals and 41 microorganisms living in land and water ecosystems. The peroxide moiety exists as both cyclic and acyclic entities and can include 1,2-dioxolanes, 1,2-dioxane rings and common secondary metabolites with a peroxo group. These peroxides possessed diverse bioactivities including anticancer, antimalarial, antimicrobial, anti-inflammatory, neuroprotective, adipogenic suppressor, antituberculosis, anti-melanogenic and anti-coagulant agents. Biosynthetic pathways and mechanisms of most endoperoxides have not been well established. Method development in peroxide detection has been a challenging task requiring multidisciplinary investigation and exploration on peroxy-containing secondary metabolites are necessary.

Streptomyces Endophytes in Edible Plants: New Insights into their Chemistry and Health Benefits.

Streptomyces is the largest source of microbial antibiotics with about 50 % of marketed antimicrobial drugs originating from this genus. Endophytic streptomyces are the link between medicinal plants and the microbial world. Endophytic Streptomyces in edible plants were not targeted before despite their uniqueness and importance. In this review, we analyzed the chemical diversity of more than 150 compounds belonging to endophytic Streptomyces chemical classes such as alkaloids, polyketides, peptides, macrolides and terpenes and their biological activities. This analysis showed a dominant antimicrobial effect for most of the isolated compounds and highlighted an underestimated diversity to be studied or repurposed for other biological activities. Return to edible plants use and conducting toxicity studies to rationalize their nutraceutical potential based on their beneficial endophytes is urged. Although there are many studies for non-vertebrates, the nutraceutical potential of these plants is expected to improve the gut microbiota since they are enriched with bioactive compounds from streptomyces species. This is the first review to discuss edible plants associated streptomyces, and we prospect that many studies will follow to unravel the mysterious health benefits of streptomyces in the human microbiome and encourage the revival of a correct lifestyle for the sake of a healthier microbiome.

Health Benefits of Antioxidant Bioactive Compounds in Ginger (Zingiber officinale) Leaves by Network Pharmacology Analysis Combined with Experimental Validation.

Network pharmacology is an ideal tool to explore the effects of therapeutic components derived from plants on human metabolic diseases that are linked to inflammation. This study investigated the antioxidant effects of ginger leaves (GLs) and predicted targets for antioxidant activity. Quantitative and free radical scavenging analyses were performed to detect the main bioactive compounds of GLs and evaluate their antioxidant activities. Chemical diversity and network pharmacology approaches were used to predict key antioxidant components of GLs and their molecular targets. Nine major bioactive compounds of GLs were quantified using an internal standard method, and the antioxidant activity was evaluated using the DPPH and ABTS free radical scavenging methods. We first built the compound-gene-pathways and protein-protein interaction networks of GLs-related antioxidant targets and then conducted gene ontology and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analyses. Molecular docking results show that astragalin, a compound isolated from GLs, had the highest level of connectivity in the compound-target network and was involved in inflammation-related biosynthesis by directly impacting cytokine gene expression and PTGS2 inhibition markers. These findings not only suggest that the compounds isolated from GLs can be developed as potential antioxidants, but also demonstrate the applicability of network pharmacology to assess the potential of foods for disease treatment.

Chemical diversity, traditional uses, and bioactivities of Rosa roxburghii Tratt: A comprehensive review.

Rosa roxburghii Tratt (RRT), known as chestnut rose, has been a subject of growing interest because of its diverse chemical composition and wide range of traditional uses. This comprehensive review aimed to thoroughly examine RRT, including its traditional applications, chemical diversity, and various bioactivities. The chemical profile of this plant is characterized by the presence of essential nutrients such as vitamin C (ascorbic acid), flavonoids, triterpenes, organic acids, tannins, phenolic compounds, polysaccharides, carotenoids, triterpenoids, volatile compounds, amino acids, and essential oils. These constituents contribute to the medicinal and nutritional value. Additionally, we explore the multifaceted bioactivities of RRT, including its potential as an anticancer agent, antioxidant, antiaging agent, antiatherogenic agent, hypoglycemic agent, immunoregulatory modulator, radioprotective agent, antimutagenic agent, digestive system regulator, anti-inflammatory agent, cardioprotective agent, and antibacterial agent, and its intriguing role in modulating the gut microbiota. Furthermore, we discuss the geographical distribution and genetic diversity of this plant species and shed light on its ecological significance. This comprehensive review provides a holistic understanding of RRT, bridges traditional knowledge with contemporary scientific research, and highlights its potential applications in medicine, nutrition, and pharmacology.

Sesquilignans: Current research and potential prospective.

Lignans are widely distributed in nature, primarily found in the xylem and resins of plants, with the constituent units C6-C3, and their dimers are the most common in plants. In recent years, the trimeric sesquilignans have also received increasing attention from scholars. More than 200 derivatives have been isolated and identified from nearly 50 families, most of which are different types (monoepoxy lignans, bisepoxy lignans, benzofuran lignans) connected with simple phenylpropanoids through ether bonds, C-C bonds, and oxygen-containing rings to constitute sesquilignans. Some of them also possess pharmacological properties, including antioxidants, hepatoprotectives, antitumors, anti-inflammatory properties, and other properties. In addition, the chemical structure of sesquilignans is closely related to the pharmacological activity, and chemical modification of methoxylation enhances the pharmacological activity. In contrast, phenolic hydroxyl and hydroxyl glycosides reduce the pharmacological activity. Therefore, the present review aims to summarize the chemical diversity, bioactivities, and constitutive relationships to provide a theoretical basis for the more profound development and utilization of sesquilignans.

Seaweeds as Nutraceutical Elements and Drugs for Diabetes Mellitus: Future Perspectives.

Diabetes mellitus is a chronic metabolic condition marked by high blood glucose levels caused by inadequate insulin synthesis or poor insulin use. This condition affects millions of individuals worldwide and is linked to a variety of consequences, including cardiovascular disease, neuropathy, nephropathy, and retinopathy. Diabetes therapy now focuses on controlling blood glucose levels through lifestyle changes, oral medicines, and insulin injections. However, these therapies have limits and may not successfully prevent or treat diabetic problems. Several marine-derived chemicals have previously demonstrated promising findings as possible antidiabetic medicines in preclinical investigations. Peptides, polyphenols, and polysaccharides extracted from seaweeds, sponges, and other marine species are among them. As a result, marine natural products have the potential to be a rich source of innovative multitargeted medications for diabetes prevention and treatment, as well as associated complications. Future research should focus on the chemical variety of marine creatures as well as the mechanisms of action of marine-derived chemicals in order to find new antidiabetic medicines and maximize their therapeutic potential. Based on preclinical investigations, this review focuses on the next step for seaweed applications as potential multitargeted medicines for diabetes, highlighting the bioactivities of seaweeds in the prevention and treatment of this illness.

Biochemical analysis of the TPS-a subfamily in Medicago truncatula.

Terpenes are important mediators of plant chemical response to environmental cues. Here, we describe the genome-wide identification and biochemical characterization of TPS-a members in Medicago truncatula, a model legume crop. Genome mining identified thirty-nine full-length terpene synthases with a significant number predicted to produce monoterpenes and sesquiterpenes. Biochemical characterization of the TPS-a subfamily associated with sesquiterpene biosynthesis revealed such compounds, that exhibit substantial biological activity in other plants. Gene expression analysis using qPCR and the Medicago gene atlas illustrated distinct tissue and time-based variation in expression in leaves and roots. Together our work establishes the gene-to-metabolite relationships for sesquiterpene synthases in M. truncatula. Understanding the biosynthetic capacity is a foundational step to defining the ecological roles of this important family of compounds.

Quantifying terpenes in tomato leaf extracts from different species using gas chromatography-mass spectrometry (GC-MS).

Terpenes play a vital role in plant defense; tomato plants produce a diverse range of terpenes within specialized glandular trichomes, influencing interactions with herbivores, predators, and pollinators. This study employed two distinct methods, namely leaf dip and maceration, to extract trichomes from tomato leaves. Terpene quantification was carried out using Gas Chromatography-Mass Spectrometry (GC-MS). The leaf dip method proved effective in selectively targeting trichome content, revealing unique extraction patterns compared to maceration. The GC-MS method demonstrated high linearity, accuracy, sensitivity, and low limits of detection and quantification. Application of the method to different tomato species (Solanum pennellii, Solanum pimpinellifolium, Solanum galapagense, Solanum habrochaites, and Solanum lycopersicum) identified significant variation in terpene content among these species, highlighting the potential of specific accessions for breeding programs. Notably, the terpene α-zingiberene, known for its repellency against whiteflies, was found in high quantities (211.90-9155.13 µg g-1) in Solanum habrochaites accession PI209978. These findings provide valuable insights into terpenoid diversity for plant defense mechanisms, guiding future research on developing pest-resistant tomato cultivars. Additionally, the study underscores the broader applications of terpenes in agriculture.

Viral Infection Induces Changes to the Metabolome, Immune Response and Development of a Generalist Insect Herbivore.

Host plant consumption and pathogen infection commonly influence insect traits related to development and immunity, which are ultimately reflected in the behavior and physiology of the insect. Herein, we explored changes in the metabolome of a generalist insect herbivore, Vanessa cardui (Lepidoptera: Nymphalidae), in response to both dietary variation and pathogen infection in order to gain insight into tritrophic interactions for insect metabolism and immunity. Caterpillars were reared on two different host plants, Plantago lanceolata (Plantaginaceae) and Taraxacum officinale (Asteraceae) and subjected to a viral infection by Junonia coenia densovirus (JcDV), along with assays to determine the insect immune response and development. Richness and diversity of plant and caterpillar metabolites were evaluated using a liquid chromatography-mass spectrometry approach and showed that viral infection induced changes to the chemical content of V. cardui hemolymph and frass dependent upon host plant consumption. Overall, the immune response as measured by phenoloxidase (PO) enzymatic activity was higher in individuals feeding on P. lanceolata compared with those feeding on T. officinale. Additionally, infection with JcDV caused suppression of PO activity, which was not host plant dependent. We conclude that viral infection combined with host plant consumption creates a unique chemical environment, particularly within the insect hemolymph. Whether and how these metabolites contribute to defense against viral infection is an open question in chemical ecology.

The chemical succession in anoxic lake waters as source of molecular diversity of organic matter.

The aquatic networks that connect soils with oceans receive each year 5.1 Pg of terrestrial carbon to transport, bury and process. Stagnant sections of aquatic networks often become anoxic. Mineral surfaces attract specific components of organic carbon, which are released under anoxic conditions to the pool of dissolved organic matter (DOM). The impact of the anoxic release on DOM molecular composition and reactivity in inland waters is unknown. Here, we report concurrent release of iron and DOM in anoxic bottom waters of northern lakes, removing DOM from the protection of iron oxides and remobilizing previously buried carbon to the water column. The deprotected DOM appears to be highly reactive, terrestrially derived and molecularly distinct, generating an ambient DOM pool that relieves energetic constraints that are often assumed to limit carbon turnover in anoxic waters. The Fe-to-C stoichiometry during anoxic mobilization differs from that after oxic precipitation, suggesting that up to 21% of buried OM escapes a lake-internal release-precipitation cycle, and can instead be exported downstream. Although anoxic habitats are transient and comprise relatively small volumes of water on the landscape scale, our results show that they may play a major role in structuring the reactivity and molecular composition of DOM transiting through aquatic networks and reaching the oceans.

The potential of marine-derived piperazine alkaloids: Sources, structures and bioactivities.

Marine-derived piperazine alkaloids (MDPAs) constitute a significant group of natural compounds known for their diverse structures and biological activities. Over the past five decades, substantial efforts have been devoted to isolating these alkaloids from marine sources and characterizing their chemical and bioactive profiles. To date, a total of 922 marine-derived piperazine alkaloids have been reported from various marine organisms. These compounds demonstrate a wide range of pharmacological properties, including cytotoxicity, antibacterial, antifungal, antiviral, and various other activities. Notably, among these activities, cytotoxicity emerges as the most prominent characteristic of marine-derived piperazine alkaloids. This review also summarizes the structure-activity relationship (SAR) studies associated with the cytotoxicity of these compounds. In summary, our objective is to provide an overview of the research progress concerning marine-derived piperazine alkaloids, with the aim of fostering their continued development and utilization.

Depicting the genetic and metabolic panorama of chemical diversity in the tea plant.

As a frequently consumed beverage worldwide, tea is rich in naturally important bioactive metabolites. Combining genetic, metabolomic and biochemical methodologies, here, we present a comprehensive study to dissect the chemical diversity in tea plant. A total of 2837 metabolites were identified at high-resolution with 1098 of them being structurally annotated and 63 of them were structurally identified. Metabolite-based genome-wide association mapping identified 6199 and 7823 metabolic quantitative trait loci (mQTL) for 971 and 1254 compounds in young leaves (YL) and the third leaves (TL), respectively. The major mQTL (i.e., P < 1.05 × 10-5, and phenotypic variation explained (PVE) > 25%) were further interrogated. Through extensive annotation of the tea metabolome as well as network-based analysis, this study broadens the understanding of tea metabolism and lays a solid foundation for revealing the natural variations in the chemical composition of the tea plant. Interestingly, we found that galloylations, rather than hydroxylations or glycosylations, were the largest class of conversions within the tea metabolome. The prevalence of galloylations in tea is unusual, as hydroxylations and glycosylations are typically the most prominent conversions of plant specialized metabolism. The biosynthetic pathway of flavonoids, which are one of the most featured metabolites in tea plant, was further refined with the identified metabolites. And we demonstrated the further mining and interpretation of our GWAS results by verifying two identified mQTL (including functional candidate genes CsUGTa, CsUGTb, and CsCCoAOMT) and completing the flavonoid biosynthetic pathway of the tea plant.

Evolution and chemical diversity of the volatile compounds in Salvia species.

INTRODUCTION: The plant essential oils are composed of volatile compounds and have significant value in preventing and treating neurological diseases, anxiety, depression, among others. The genus Salvia has been shown to be an important medicinal resource, especially the aerial parts of genus Salvia, which are rich in volatile compounds; however, the chemical diversity and distribution patterns of volatile compounds in Salvia species are still unknown. OBJECTIVE: The work is performed to analyse the chemical diversity and distribution patterns of volatile compounds in genus Salvia. METHODS: The genomic single nucleotide polymorphisms (SNPs) combined with gas chromatography-mass spectrometry (GC-MS) were used to explore the evolution and chemical diversity of Salvia volatile compounds. Initially, the genetic relationship of genus Salvia was revealed by phylogenetic tree that was constructed based on SNPs. And then, GC-MS was applied to explore the chemical diversity of volatile compounds. RESULTS: The results indicated that the volatile compounds were mainly monoterpenoids, sesquiterpenoids, and aliphatic compounds. The genomic SNPs divided species involved in this work into four branches. The volatile compounds in the first and second branches were mainly sesquiterpenoids and monoterpenoids, respectively. Species in the third branch contained more aliphatic compounds and sesquiterpenoids. And those in the fourth branch were also rich in monoterpenoids but had relatively simple chemical compositions. CONCLUSION: This study offered new insights into the phylogenetic relationships besides chemistry diversity and distribution pattern of volatile compounds of genus Salvia, providing theoretical guidance for the investigations and development of secondary metabolites.

Assessment of the chemical and genetic variability among accessions of Cicerbita alpina (L.) Wallr., an alpine plant with anthelmintic properties.

Cicerbita alpina (L.) Wallr, is a perennial alpine plant and a member of the Asteraceae family, typically found at altitudes above 1000 meters in the Italian Alps. Although previously utilized primarily as a local delicacy, recent studies have revealed strong antiparasitic activity through in vitro experiments. In Europe, numerous chemical drugs employed to combat nematodes - helminths that infest the digestive tract of livestock - are banned due to their environmental harm or show only reduced efficiency because of the development of resistance. Consequently, there is a growing demand for new alternative anthelmintic treatments in agricultural practices. Specialized metabolites found in the extracts of C. alpina could offer a sustainable and biological alternative to chemical drugs, specifically for nematode control. For this purpose, a unique germplasm collection originating from eight distinct natural populations in the Italian Alps was analyzed for its chemical diversity using state-of-the-art targeted LC-MS/MS spectrometry, including quantification based on multiple reaction monitoring. The predominant metabolites identified from the species were the caffeic acid derivatives chicoric acid, chlorogenic acid, and 3. 5-dicaffeoylquinic acid, the sesquiterpene lactone derivative 8-O-acetyl-15-ß-D-glucopyranosyl lactucin and the flavone glycosides, apigenin-7-O-glucoside and luteolin-7-O-glucoside, alongside their precursors apigenin and luteolin, respectively. Additionally, the genetic diversity of eighty individual plants within the germplasm collection was evaluated using ten DNA molecular markers (Simple Sequence Repeats), successfully transferred from two closely related species (Cichorium intybus and Tanacetum parthenium). This investigation unveiled a significant range of genetic diversity within the examined populations, resulting in the establishment of three distinct genetic groups. The findings were further correlated with the original ecological environment and local climate conditions spanning a biennial period, indicating substantial variations among the different accessions and the intricate interplay between genetic background and environmental factors. These results could serve as a basis for future domestication of the species through plant breeding programs ensuring product quality, but also facilitating the cultivation of C. alpina in more diverse geographic regions.

Plant diversity and soil legacy independently affect the plant metabolome and induced responses following herbivory.

Plant and soil biodiversity can have significant effects on herbivore resistance mediated by plant metabolites. Here, we disentangled the independent effects of plant diversity and soil legacy on constitutive and herbivore-induced plant metabolomes of three plant species in two complementary microcosm experiments. First, we grew plants in sterile soil with three different plant diversity levels. Second, single plant species were grown on soil with different plant diversity-induced soil legacies. We infested a subset of all plants with Spodoptera exigua larvae, a generalist leaf-chewing herbivore, and assessed foliar and root metabolomes. Neither plant diversity nor soil legacy had significant effects on overall foliar, root, or herbivore-induced metabolome composition. Herbivore-induced metabolomes, however, differed from those of control plants. We detected 139 significantly regulated metabolites by comparing plants grown in monocultures with conspecifics growing in plant or soil legacy mixtures. Moreover, plant-plant and plant-soil interactions regulated 141 metabolites in herbivore-induced plants. Taken together, plant diversity and soil legacy independently alter the concentration and induction of plant metabolites, thus affecting the plant's defensive capability. This is a first step toward disentangling plant and soil biodiversity effects on herbivore resistance, thereby improving our understanding of the mechanisms that govern ecosystem functioning.

Co-factor independent oxidases ncnN and actVA-3 are involved in the dimerization of benzoisochromanequinone antibiotics in naphthocyclinone and actinorhodin biosynthesis.

Streptomyces produce complex bioactive secondary metabolites with remarkable chemical diversity. Benzoisochromanequinone polyketides actinorhodin and naphthocyclinone are formed through dimerization of half-molecules via single or double carbon-carbon bonds, respectively. Here we sequenced the genome of S. arenae DSM40737 to identify the naphthocyclinone gene cluster and established heterologous production in S. albus J1074 by utilizing direct cluster capture techniques. Comparative sequence analysis uncovered ncnN and ncnM gene products as putative enzymes responsible for dimerization. Inactivation of ncnN that is homologous to atypical co-factor independent oxidases resulted in the accumulation of fogacin, which is likely a reduced shunt product of the true substrate for naphthocyclinone dimerization. In agreement, inactivation of the homologous actVA-3 in S. coelicolor M145 also led to significantly reduced production of actinorhodin. Previous work has identified the NAD(P)H-dependent reductase ActVA-4 as the key enzyme in actinorhodin dimerization, but surprisingly inactivation of the homologous ncnM did not abolish naphthocyclinone formation and the mutation may have been complemented by an endogenous gene product. Our data suggests that dimerization of benzoisochromanequinone polyketides require two-component reductase-oxidase systems.