Metabolism Of Medicinal Plants Research Articles

Actinobacteria: Smart Micro-Factories for The Health Sector.

Antibiotics are considered "wonder drugs" due to the fact that they are the most extensively utilised medication in the world. They are used to cure a broad spectrum of diseases and lethal infections. A variety of bacteria and fungi produce antibiotics as a result of secondary metabolism; however, their production is dominated by a special class of bacteria, namely Actinobacteria. Actinobacteria are gram-positive bacteria with high G+C content and unparalleled antibiotic-producing ability. They produce numerous polyenes, tetracyclines, β-lactams, macrolides, and peptides. Actinobacteria are ubiquitous in nature and are isolated from various sources, such as marine and terrestrial endophytes of plants and air. They are studied for their relative antibiotic-producing ability along with the mechanism that the antibiotics follow to annihilate the pathogenic agents that include bacteria, fungi, protozoans, helminths, etc. Actinobacteria isolated from endophytes of medicinal plants have amassed significant attention as they interfere with the metabolism of medicinal plants and acquire enormous benefits from it in the form of conspicuous novel antibiotic-producing ability. Actinobacteria is not only an antibiotic but also a rich source of anticancer compounds that are widely used owing to its remarkable tumorigenic potential. Today, amongst Actinobacteria, class Streptomyces subjugates the area of antibiotic production, producing 70% of all known antibiotics. The uniqueness of bioactive Actinobacteria has turned the attention of scientists worldwide in order to explore its potentiality as effective "micronanofactories". This study provides a brief overview of the production of antibiotics from Actinobacteria inhabiting diverse environments and the methods involved in the screening of antibiotics.

Nitrogen Sources Reprogram Carbon and Nitrogen Metabolism to Promote Andrographolide Biosynthesis in Andrographis paniculata (Burm.f.) Nees Seedlings.

Carbon (C) and nitrogen (N) metabolisms participate in N source-regulated secondary metabolism in medicinal plants, but the specific mechanisms involved remain to be investigated. By using nitrate (NN), ammonium (AN), urea (UN), and glycine (GN), respectively, as sole N sources, we found that N sources remarkably affected the contents of diterpenoid lactone components along with C and N metabolisms reprograming in Andrographis paniculata, as compared to NN, the other three N sources raised the levels of 14-deoxyandrographolide, andrographolide, dehydroandrographolide (except UN), and neoandrographolide (except AN) with a prominent accumulation of farnesyl pyrophosphate (FPP). These N sources also raised the photosynthetic rate and the levels of fructose and/or sucrose but reduced the activities of phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoenolpyruvate carboxylase (PEPC) and pyruvate dehydrogenase (PDH). Conversely, phosphoenolpyruvate carboxykinase (PEPCK) and malate enzyme (ME) activities were upregulated. Simultaneously, citrate, cis-aconitate and isocitrate levels declined, and N assimilation was inhibited. These results indicated that AN, UN and GN reduced the metabolic flow of carbohydrates from glycolysis into the TCA cycle and downstream N assimilation. Furthermore, they enhanced arginine and GABA metabolism, which increased C replenishment of the TCA cycle, and increased ethylene and salicylic acid (SA) levels. Thus, we proposed that the N sources reprogrammed C and N metabolism, attenuating the competition of N assimilation for C, and promoting the synthesis and accumulation of andrographolide through plant hormone signaling. To obtain a higher production of andrographolide in A. paniculata, AN fertilizer is recommended in its N management.

A Cotyledon-based Virus-Induced Gene Silencing (Cotyledon-VIGS) approach to study specialized metabolism in medicinal plants

BackgroundVirus-induced gene silencing (VIGS) is widely used in plant functional genomics. However, the efficiency of VIGS in young plantlets varies across plant species. Additionally, VIGS is not optimized for many plant species, especially medicinal plants that produce valuable specialized metabolites.ResultsWe evaluated the efficacy of five-day-old, etiolated seedlings of Catharanthus roseus (periwinkle) for VIGS. The seedlings were vacuum-infiltrated with Agrobacterium tumefaciens GV3101 cells carrying the tobacco rattle virus (TRV) vectors. The protoporphyrin IX magnesium chelatase subunit H (ChlH) gene, a key gene in chlorophyll biosynthesis, was used as the target for VIGS, and we observed yellow cotyledons 6 days after infiltration. As expected, the expression of CrChlH and the chlorophyll contents of the cotyledons were significantly decreased after VIGS. To validate the cotyledon based-VIGS method, we silenced the genes encoding several transcriptional regulators of the terpenoid indole alkaloid (TIA) biosynthesis in C. roseus, including two activators (CrGATA1 and CrMYC2) and two repressors (CrGBF1 and CrGBF2). Silencing CrGATA1 led to downregulation of the vindoline pathway genes (T3O, T3R, and DAT) and decreased vindoline contents in cotyledons. Silencing CrMYC2, followed by elicitation with methyl jasmonate (MeJA), resulted in the downregulation of ORCA2 and ORCA3. We also co-infiltrated C. roseus seedlings with TRV vectors that silence both CrGBF1 and CrGBF2 and overexpress CrMYC2, aiming to simultaneous silencing two repressors while overexpressing an activator. The simultaneous manipulation of repressors and activator resulted in significant upregulation of the TIA pathway genes. To demonstrate the broad application of the cotyledon-based VIGS method, we optimized the method for two other valuable medicinal plants, Glycyrrhiza inflata (licorice) and Artemisia annua (sweet wormwood). When TRV vectors carrying the fragments of the ChlH genes were infiltrated into the seedlings of these plants, we observed yellow cotyledons with decreased chlorophyll contents.ConclusionsThe widely applicable cotyledon-based VIGS method is faster, more efficient, and easily accessible to additional treatments than the traditional VIGS method. It can be combined with transient gene overexpression to achieve simultaneous up- and down-regulation of desired genes in non-model plants. This method provides a powerful tool for functional genomics of medicinal plants, facilitating the discovery and production of valuable therapeutic compounds.

Abiotic factors and endophytes co-regulate flavone and terpenoid glycoside metabolism in Glycyrrhiza uralensis

Recently, endorhizospheric microbiota is realized to be able to promote the secondary metabolism in medicinal plants, but the detailed metabolic regulation metabolisms and whether the promotion is influenced by environmental factors are unclear yet. Here, the major flavonoids and endophytic bacterial communities in various Glycyrrhiza uralensis Fisch. roots collected from seven distinct places in northwest China, as well as the edaphic conditions, were characterized and analyzed. It was found that the soil moisture and temperature might modulate the secondary metabolism in G. uralensis roots partially through some endophytes. One rationally isolated endophyte Rhizobium rhizolycopersici GUH21 was proved to promote the accumulation of isoliquiritin and glycyrrhizic acid significantly in roots of the potted G. uralensis under the relatively high-level watering and low temperature. Furthermore, we did the comparative transcriptome analysis of G. uralensis seedling roots in different treatments to investigate the detailed mechanisms of the environment-endophyte-plant interactions and found that the low temperature went hand in hand with the high-level watering to activate the aglycone biosynthesis in G. uralensis, while GUH21 and the high-level watering cooperatively promoted the in planta glucosyl unit production. Our study is of significance for the development of methods to rationally promote the medicinal plant quality.Key points• Soil temperature and moisture related to isoliquiritin contents in Glycyrrhiza uralensis Fisch.• Soil temperature and moisture related to the hosts’ endophytic bacterial community structures.• The causal relation among abiotic factors—endophytes—host was proved through the pot experiment.

Contributions of Beneficial Microorganisms in Soil Remediation and Quality Improvement of Medicinal Plants

Medicinal plants (MPs) are important resources widely used in the treatment and prevention of diseases and have attracted much attention owing to their significant antiviral, anti-inflammatory, antioxidant and other activities. However, soil degradation, caused by continuous cropping, excessive chemical fertilizers and pesticide residues and heavy metal contamination, seriously restricts the growth and quality formation of MPs. Microorganisms, as the major biota in soil, play a critical role in the restoration of the land ecosystem. Rhizosphere microecology directly or indirectly affects the growth and development, metabolic regulation and active ingredient accumulation of MPs. Microbial resources, with the advantages of economic efficiency, harmless to environment and non-toxic to organisms, have been recommended as a promising alternative to conventional fertilizers and pesticides. The introduction of beneficial microbes promotes the adaptability of MPs to adversity stress by enhancing soil fertility, inhibiting pathogens and inducing systemic resistance. On the other hand, it can improve the medicinal quality by removing soil pollutants, reducing the absorption and accumulation of harmful substances and regulating the synthesis of secondary metabolites. The ecological and economic benefits of the soil microbiome in agricultural practices are increasingly recognized, but the current understanding of the interaction between soil conditions, root exudates and microbial communities and the mechanism of rhizosphere microecology affecting the secondary metabolism of MPs is still quite limited. More research is needed to investigate the effects of the microbiome on the growth and quality of different medicinal species. Therefore, the present review summarizes the main soil issues in medicinal plant cultivation, the functions of microbes in soil remediation and plant growth promotion and the potential mechanism to further guide the use of microbial resources to promote the ecological cultivation and sustainable development of MPs.

Morphological, physiological, and secondary metabolic responses of Taraxacum officinale to salt stress

Salt stress has a major effect on growth and secondary metabolism in medicinal plants, however, the effect of salt stress on Taraxacum officinale F. H. Wigg. is still scarce. In this study, we evaluated the effects of salt stress on the physiology, morphology, phenolic acid accumulation, and expression of genes involved in phenolic acid biosynthesis in T. officinale. We found that plants grew well at 1 g kg−1 NaCl, and the state of photosystem Ⅱ (PSⅡ) and the organization of the chloroplasts at 0.5 g kg−1 NaCl showed no significant differences compared with the control. However, 2 g kg−1 and 4 g kg−1 NaCl inhibited growth and accelerated leaf senescence. At 4 g kg−1 NaCl, the fresh and dry weights decreased to 28% and 42% of the control, while chlorosis and necrosis were observed on the leaves. Furthermore, up-regulation of the expression of ToC3′H corresponded with an increase in the levels of caffeoylquinic acids (chlorogenic acid and isochlorogenic acid A) at NaCl concentration ≤ 1 g kg−1. Expressions of four phenolic acid biosynthesis genes, ToC4H, To4CL, ToHCT, and ToHQT, were down-regulated with increasing NaCl concentrations, consistent with the observed decreases in caftaric and cichoric acids. In summary, cultivation of T. officinale under mild salt stress (NaCl ≤ 1 g kg−1) is feasible and facilitates the accumulation of caffeoylquinic acids; thus this species may be recommended for saline soils.

Co-Expression Analysis Reveals Differential Expression of Homologous Genes Associated with Specific Terpenoid Biosynthesis in Rehmannia glutinosa.

Terpenoids are naturally occurring compounds involved in respiration, photosynthesis, membrane fluidity, and pathogen interactions and are classified according to the structure of their carbon skeleton. Although most terpenoids possess pharmacological activity, knowledge about terpenoid metabolism in medicinal plants is insufficient. Rehmannia glutinosa (R. glutinosa) is a traditional herb that is widely used in East Asia and has been reported to contain various terpenoids. In this study, we performed a comprehensive transcriptome analysis of terpenoid metabolism in R. glutinosa using two RNA sequencing platforms: Illumina and PacBio. The results show that the sterol, saponin, iridoid, and carotenoid pathways are active in R. glutinosa. Sterol and saponin biosynthesis were mevalonate pathway dependent, whereas iridoid and carotenoid biosynthesis were methylerythritol 4-phosphate pathway dependent. In addition, we found that the homologous genes of key enzymes involved in terpenoid metabolism were expressed differentially and that the differential expression of these genes was associated with specific terpenoid biosynthesis. The different expression of homologous genes encoding acetyl-CoA acetyltransferase, 3-hydroxy-3-methylglutaryl-CoA reductase, mevalonate kinase, mevalonate diphosphate decarboxylase, farnesyl pyrophosphate synthase, squalene synthase, and squalene epoxidase was associated with sterol and saponin biosynthesis. Homologous genes encoding 1-deoxy-D-xylulose 5-phosphate synthase were also differentially expressed and were associated with carotenoid and iridoid biosynthesis. These results suggest that the biosynthesis of specific terpenoids can be regulated by the homologous of key enzymes involved in plant terpenoid metabolism.

Applications of cell- and tissue-specific 'omics to improve plant productivity.

The individual tissues and cell types of plants each have characteristic properties that contribute to the function of the plant as a whole. These are reflected by unique patterns of gene expression, protein and metabolite content, which enable cell-type-specific patterns of growth, development and physiology. Gene regulatory networks act within the cell types to govern the production and activity of these components. For the broader organism to grow and reproduce successfully, cell-type-specific activity must also function within the context of surrounding cell types, which is achieved by coordination of signalling pathways. We can investigate how gene regulatory networks are constructed and function using integrative ‘omics technologies. Historically such experiments in plant biological research have been performed at the bulk tissue level, to organ resolution at best. In this review, we describe recent advances in cell- and tissue-specific ‘omics technologies that allow investigation at much improved resolution. We discuss the advantages of these approaches for fundamental and translational plant biology, illustrated through the examples of specialised metabolism in medicinal plants and seed germination. We also discuss the challenges that must be overcome for such approaches to be adopted widely by the community.

Virus-Induced Gene Silencing for Functional Genomics of Specialized Metabolism in Medicinal Plants.

Virus-induced gene silencing (VIGS) is a functional genomics tool to transiently downregulate the expression of target gene(s) by exploiting the plant's innate defense mechanism against invading RNA viruses. VIGS is a rapid and efficient approach to analyze the gene function, particularly, in the plants that are not amenable to stable genetic transformation. This strategy has been successfully used to decipher the function of several genes and transcription factors involved in the biosynthesis of specialized metabolites and regulation of specialized metabolism, respectively, in different medicinal and aromatic plants. Here, we describe a detailed Tobacco rattle virus (TRV)-mediated VIGS protocol for silencing of the gene encoding Phytoene desaturase (PDS) in important medicinal plants Catharanthus roseus, Calotropis gigantean, Rauwolfia serpentina, and Ocimum basilicum. Our methods allow the study of gene function within 3-4weeks after agro-inoculation, and can be an easy and efficient approach for future studies on understanding of the biosynthesis of specialized metabolites in these important medicinal plants.

Salinity stress alters ion homeostasis, antioxidant activities and the production of rosmarinic acid, luteolin and apigenin in Dracocephalum kotschyi Boiss

Salt stress affects growth and secondary metabolism in medicinal plants. There is no information about the impacts of salt stress on Dracocephalum kotschyi Boiss. Therefore, in this study, the 60-day old seedlings grown in coco peat and perlite were irrigated with various concentrations of NaCl (0, 25, 50, 75, and 100 mM) in accordance with a randomized complete block design for 3 weeks. The results showed that with increasing salt concentration, Na+ concentration was increased, but Ca2+ and K+ concentrations and fresh and dry weights were decreased in both roots and shoots. Besides, photosynthetic pigments and relative water content declined, whereas proline concentration and electrolyte leakage levels elevated in leaves under salinity stress. The activities of ascorbate peroxidase and guaiacol peroxidase enzymes were enhanced at lower salt concentrations but impaired under higher concentrations of NaCl. High-performance liquid chromatography showed that the contents of rosmarinic acid, luteolin, and apigenin were increased with aggravation of salt stress. The highest total phenolic and flavonoid contents and the rosmarinic acid, luteolin, and apigenin contents were verified at 75 mM NaCl that was concomitant with the most 2,2-diphenylpicrylhydrazyl scavenging activity in the leaves. In contrast, all these attributes decreased under 100 mM NaCl. In conclusion, the results unveiled that D. kotschyi is a moderate salt-tolerant plant and adaptive mechanisms adopted by this plant are including Na+ exclusion in roots, the activation of the antioxidant system, and the alteration of phenolic profile. This study also suggests that mild to moderate salinity can be employed as an elicitor to increasing some pharmaceutical important phenolic compounds in D. kotschyi.

Overexpression of Ath-MIR160b increased the biomass while reduced the content of tanshinones in Salvia miltiorrhiza hairy roots by targeting ARFs genes

MicroRNAs (miRNAs) have attracted increasing attention in the field of medicinal plant research. Our previous analyses indicated that the mature miR160a level was related to the accumulation of tanshinones in Salvia miltiorrhiza (S. miltiorrhiza). Therefore, the aim of this research was to reveal how the miR160a regulates the tanshinones biosynthesis. The overexpression of miR160a in hairy roots of S. miltiorrhiza down-regulated the levels of the target genes ARF10, 16, and 17, and inhibited tanshinones biosynthesis but increased hairy root biomass. In overexpression line 1, the content of four major tanshinones dropped sharply to 9.06% (dihydrotanshinone I), 12.56% (cryptotanshinone), 12.02% (tanshinone I), and 8.52% (tanshinone IIA) compared with that of the wildtype (WT). The fresh weight (FW) of hairy roots increased to 1.72-fold of the WT, and in overexpression lines 4, tanshinones were not detected. However, the FW of hairy roots in overexpression line 4 increased to 1.90-fold of the WT. We also observed the down regulated genes in the tanshinones biosynthesis pathway. In particular, the transcription level of KSL2 dropped to 3% as compared to the WT, which was consistent with the decrease in tanshinones content. We further analyzed hormone changes and found an increase in indole acetic acid accumulation, while the accumulation of salicylic acid (SA) and jasmonic acid (JA) decreased. These findings indicate that miR160a may negatively regulate the biosynthesis of tanshinones, while promote the growth of hairy roots by targeting ARF10, 16, and 17. Our findings demonstrate that miRNAs could be used as an alternative strategy to dissect the complex network of secondary metabolism in medicinal plants. MiR160a overexpression promoted the IAA level and the growth of hairy roots of Salvia miltiorrhiza, but reduced the GH3-like level and production of tanshinones by targeting ARF10, ARF16, and ARF17.

Computational screening of miRNAs and their targets in leaves of Hypericum spp. by transcriptome-mining: a pilot study.

Our work provides a survey of mature miRNAs, their target genes and primary precursors identified by in-silico approach in leaf transcriptomes of five selected Hypericum species. MiRNAs are small non-coding RNA molecules found in animals, terrestrial plants, several algae and molds. As their role lies in the post-transcriptional gene silencing, these tiny molecules regulate many biological processes. Phyto-miRNAs are considered the important regulators of secondary metabolism in medicinal plants. The genus Hypericum comprises many producers of bioactive compounds, mainly unique naphtodianthrones with a great therapeutic potential. The main goal of our work was to identify genetically conserved miRNAs, characterize their primary precursors and target sequences in the leaf transcriptomes of five Hypericum species using in-silico approach. We found 20 sequences of potential Hypericum pri-miRNAs, and predicted and computationally validated their secondary structures. The mature miRNAs were identified by target genes screening analysis. Whereas predicted miRNA profiles differed in less genetically conserved families, the highly conserved miRNAs were found in almost all studied species. Moreover, we detected several novel highly likely miRNA-mRNA interactions, such as mir1171 with predicted regulatory role in the biosynthesis of melatonin in plants. Our work contributes to the knowledge of Hypericum miRNAome and miRNA-mRNA interactions.

Potential Effect of Pegagan (Centella asiatica (L.) Urban) and Widuri (Calotropis gigantea (L.)) as Immunomodulator

Abstract: The immune system functions to protect the body from pathogens and cure disease. Even a mild infection will have a bad effect if the host's immune system is not working properly. Modification of the immune response functions to increase and decrease the immune response to overcome disease known as immunomodulation. Immunomodulators are used either as a prevention or treatment of various diseases related to immune disorders. Immunomodulatory drugs change the immune system response by increasing (immunostimulating) or decreasing (immunosuppressive) antibody production. Immunostimulators are given to increase the immune response to infectious diseases, immunodeficiency (e.g. AIDS) and cancer. Immunosuppressive drugs are used to reduce the immune response to transplanted organs and treat autoimmune diseases. The use of medicinal plants to treat various diseases has shown minimal side effects. Natural compounds that are produced from the metabolism of medicinal plants are known to affect the immune system, both the function and production of immune cells, as well as antibody secretion. Indonesia is one of the countries that has used plants as traditional medicine since ancient times. Indonesia 7,000 species of medicinal plants that have been studied to address health problems. Among the medicinal plants that have been studied are Centella asiatica (L.) Urban and Calotropis gigantea (L.) which have been shown to cure various diseases. This review article describes the potential of native Indonesian medicinal plants, namely Centella asiatica (L.) Urban and Calotropis gigantea (L.) as immunomodulators.

Smoke-Isolated Karrikins Stimulated Tanshinones Biosynthesis in Salvia miltiorrhiza through Endogenous Nitric Oxide and Jasmonic Acid.

Although smoke-isolated karrikins (KAR1) could regulate secondary metabolism in medicinal plants, the signal transduction mechanism has not been reported. This study highlights the influence of KAR1 on tanshinone I (T-I) production in Salvia miltiorrhiza and the involved signal molecules. Results showed KAR1-induced generation of nitric oxide (NO), jasmonic acid (JA) and T-I in S. miltiorrhiza hairy root. KAR1-induced increase of T-I was suppressed by NO-specific scavenger (cPTIO) and NOS inhibitors (PBITU); JA synthesis inhibitor (SHAM) and JA synthesis inhibitor (PrGall), which indicated that NO and JA play essential roles in KAR1-induced T-I. NO inhibitors inhibited KAR1-induced generation of NO and JA, suggesting NO was located upstream of JA signal pathway. NO-induced T-I production was inhibited by SHAM and PrGall, implying JA participated in transmitting signal NO to T-I accumulation. In other words, NO mediated the KAR1-induced T-I production through a JA-dependent signaling pathway. The results helped us understand the signal transduction mechanism involved in KAR1-induced T-I production and provided helpful information for the production of S. miltiorrhiza hairy root.

The Integration of Metabolomics and Next-Generation Sequencing Data to Elucidate the Pathways of Natural Product Metabolism in Medicinal Plants

The Integration of Metabolomics and Next-Generation Sequencing Data to Elucidate the Pathways of Natural Product Metabolism in Medicinal Plants

A Comparison of the Immunostimulatory Effects of Polysaccharides from Tetraploid and Diploid Echinacea purpurea.

Polyploidization is an effective means of improving the active components and quality of secondary metabolism in medicinal plants. In the present study, we compared the immunostimulatory effects of crude polysaccharides from tetraploid and diploid Echinacea purpurea. The results showed that the carbohydrate contents of crude polysaccharide of tetraploid E. purpurea (CPE4) and diploid E. purpurea (CPE2) were 85.51% and 44.65%, respectively. 1H-nuclear magnetic resonance (NMR) spectroscopy and gel-permeation chromatography (GPC) analyses showed no major differences in the overall structure and molecular weight of polysaccharides between CPE4 and CPE2. However, some differences in the relative content of the same polysaccharides group were observed between CPE4 and CPE2. In in vitro tests, EP4 could stimulate lymphocyte proliferation and secretion of cytokines maximally at the concentration of 0.0312 mg/mL, and EP2 could stimulate lymphocyte proliferation and secretion of cytokines maximally at the concentration of 0.125 mg/mL. In in vivo tests, EP4 was more effective at promoting the proliferation of lymphocytes and secretion of cytokines in mice immunosuppressed by cyclophosphamide than EP2 at the same concentration. Taken together, these data demonstrated that the relative content of the partial polysaccharides group is increased, and the immunoregulatory effect is enhanced in tetraploid E. purpurea.

The Integration of Metabolomics and Next-Generation Sequencing Data to Elucidate the Pathways of Natural Product Metabolism in Medicinal Plants.

Plants have always been used as medicines since ancient times to treat diseases. The knowledge around the active components of herbal preparations has remained nevertheless fragmentary: the biosynthetic pathways of many secondary metabolites of pharmacological importance have been clarified only in a few species, while the chemodiversity present in many medicinal plants has remained largely unexplored. Despite the advancements of synthetic biology for production of medicinal compounds in heterologous hosts, the native plant species are often the most reliable and economic source for their production. It thus becomes fundamental to investigate the metabolic composition of medicinal plants to characterize their natural metabolic diversity and to define the biosynthetic routes in planta of important compounds to develop strategies to further increase their content. We present here a number of case studies for selected classes of secondary metabolites and we review their health benefits and the historical developments in their structural elucidation and characterization of biosynthetic genes. We cover the cases of benzoisoquinoline and monoterpenoid indole alkaloids, cannabinoids, caffeine, ginsenosides, withanolides, artemisinin, and taxol; we show how the "early" biochemical or the more recent integrative approaches-based on omics-analyses-have helped to elucidate their metabolic pathways and cellular compartmentation. We also summarize how the knowledge generated about their biosynthesis has been used to develop metabolic engineering strategies in heterologous and native hosts. We conclude that following the advent of novel, high-throughput and cost-effective analytical technologies, the secondary metabolism of medicinal plants can now be examined under the lens of systems biology.

Core Microbiome of Medicinal Plant Salvia miltiorrhiza Seed: A Rich Reservoir of Beneficial Microbes for Secondary Metabolism?

Seed microbiome includes special endophytic or epiphytic microbial taxa associated with seeds, which affects seed germination, plant growth, and health. Here, we analyzed the core microbiome of 21 Salvia miltiorrhiza seeds from seven different geographic origins using 16S rDNA and ITS amplicon sequencing, followed by bioinformatics analysis. The whole bacterial microbiome was classified into 17 microbial phyla and 39 classes. Gammaproteobacteria (67.6%), Alphaproteobacteria (15.6%), Betaproteobacteria (2.6%), Sphingobacteria (5.0%), Bacilli (4.6%), and Actinobacteria (2.9%) belonged to the core bacterial microbiome. Dothideomycetes comprised 94% of core fungal microbiome in S. miltiorrhiza seeds, and another two dominant classes were Leotiomycetes (3.0%) and Tremellomycetes (2.0%). We found that terpenoid backbone biosynthesis, degradation of limonene, pinene, and geraniol, and prenyltransferases, were overrepresented in the core bacterial microbiome using phylogenetic examination of communities by reconstruction of unobserved states (PICRUSt) software. We also found that the bacterial genera Pantoea, Pseudomonas, and Sphingomonas were enriched core taxa and overlapped among S. miltiorrhiza, maize, bean, and rice, while a fungal genus, Alternaria, was shared within S. miltiorrhiza, bean, and Brassicaceae families. These findings highlight that seed-associated microbiomeis an important component of plant microbiomes, which may be a gene reservoir for secondary metabolism in medicinal plants.

Integrated omics analysis of specialized metabolism in medicinal plants

Medicinal plants are a rich source of highly diverse specialized metabolites with important pharmacological properties. Until recently, plant biologists were limited in their ability to explore the biosynthetic pathways of these metabolites, mainly due to the scarcity of plant genomics resources. However, recent advances in high-throughput large-scale analytical methods have enabled plant biologists to discover biosynthetic pathways for important plant-based medicinal metabolites. The reduced cost of generating omics datasets and the development of computational tools for their analysis and integration have led to the elucidation of biosynthetic pathways of several bioactive metabolites of plant origin. These discoveries have inspired synthetic biology approaches to develop microbial systems to produce bioactive metabolites originating from plants, an alternative sustainable source of medicinally important chemicals. Since the demand for medicinal compounds are increasing with the world's population, understanding the complete biosynthesis of specialized metabolites becomes important to identify or develop reliable sources in the future. Here, we review the contributions of major omics approaches and their integration to our understanding of the biosynthetic pathways of bioactive metabolites. We briefly discuss different approaches for integrating omics datasets to extract biologically relevant knowledge and the application of omics datasets in the construction and reconstruction of metabolic models.

Changing trends in biotechnology of secondary metabolism in medicinal and aromatic plants.

Medicinal and aromatic plants are known to produce secondary metabolites that find uses as flavoring agents, fragrances, insecticides, dyes and drugs. Biotechnology offers several choices through which secondary metabolism in medicinal plants can be altered in innovative ways, to overproduce phytochemicals of interest, to reduce the content of toxic compounds or even to produce novel chemicals. Detailed investigation of chromatin organization and microRNAs affecting biosynthesis of secondary metabolites as well as exploring cryptic biosynthetic clusters and synthetic biology options, may provide additional ways to harness this resource. Plant secondary metabolites are a fascinating class of phytochemicals exhibiting immense chemical diversity. Considerable enigma regarding their natural biological functions and the vast array of pharmacological activities, amongst other uses, make secondary metabolites interesting and important candidates for research. Here, we present an update on changing trends in the biotechnological approaches that are used to understand and exploit the secondary metabolism in medicinal and aromatic plants. Bioprocessing in the form of suspension culture, organ culture or transformed hairy roots has been successful in scaling up secondary metabolite production in many cases. Pathway elucidation and metabolic engineering have been useful to get enhanced yield of the metabolite of interest; or, for producing novel metabolites. Heterologous expression of putative plant secondary metabolite biosynthesis genes in a microbe is useful to validate their functions, and in some cases, also, to produce plant metabolites in microbes. Endophytes, the microbes that normally colonize plant tissues, may also produce the phytochemicals produced by the host plant. The review also provides perspectives on future research in the field.