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Special Issue "Biosynthesis and Regulatory Mechanism of Secondary Metabolites in Medicinal Plants"

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Plant Sciences".

Deadline for manuscript submissions: 31 December 2023 | Viewed by 7645

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Prof. Dr. Shanfa Lu

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Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
Interests: medicinal plant; bioactive compound; biosynthetic pathway; noncoding RNA; transcription factor; genome; transcriptome; metabolome

Special Issue Information

Dear Colleagues,

Medicinal plants are an important resource for humans. However, compared with model systems and crops, the number of studies on medicinal plants has fallen far behind the amount of research on other topics. Recently, with the increase in demand for medicinal plants and the development and application of high-throughput technologies, the research field of medicinal plants has rapidly expanded. Significant progress has been made in genomics, epigenomics, transcriptomics and metabolomics of medicinal plants. Numerous studies have contributed to the biosynthetic pathway of secondary metabolites, genes encoding key enzymes of the pathway, and regulatory mechanisms of secondary metabolism. This enables the production of secondary metabolites through metabolic engineering and synthetic biology. Moreover, novel technologies and strategies are developing and applying to this research field. This open-access Special Issue of IJMS is devoted to publishing original research and review articles on medicinal plant studies, highlighting recent advances in the biosynthesis and regulatory mechanisms of secondary metabolites, particularly significant discoveries from intensive studies, and the development and application of novel technologies. This issue aims to provide an accessible collection of research that shares the latest innovative results from the research field of medicinal plants to aid further studies on secondary metabolism, medicinal plant improvement, and the production of functionally important secondary metabolites.

Topics of this Special Issue include, but are not limited to:

Genomics, epigenomics, transcriptomics and metabolomics of medicinal plants;
Biosynthetic pathway of secondary metabolites;
Key enzyme genes involved in the biosynthesis of secondary metabolites;
Epigenetic regulation of secondary metabolism: microRNA, long noncoding RNA, DNA methylation, RNA methylation, etc.;
Transcription factor and regulatory network in medicinal plants;
Metabolic engineering and synthetic biology of secondary metabolites;
Application of high-throughput sequencing technologies;
Databases associated with the biosynthesis and regulation of secondary metabolites;
Novel technologies and strategies for secondary metabolism studies.

Prof. Dr. Shanfa Lu
Guest Editor

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Keywords

biosynthetic pathway
epigenetic regulation
high-throughput sequencing
medicinal plant
metabolic engineering
omics
regulatory mechanism
secondary metabolite
synthetic biology
transcription factor

Published Papers (7 papers)

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Research

Open AccessArticle

Synthesis of Crocin I and Crocin II by Multigene Stacking in Nicotiana benthamiana

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Int. J. Mol. Sci. 2023, 24(18), 14139; https://doi.org/10.3390/ijms241814139 - 15 Sep 2023

Viewed by 246

Abstract

Crocins are a group of highly valuable water-soluble carotenoids that are reported to have many pharmacological activities, such as anticancer properties, and the potential for treating neurodegenerative diseases including Alzheimer’s disease. Crocins are mainly biosynthesized in the stigmas of food–medicine herbs Crocus sativus L. and Gardenia jasminoides fruits. The distribution is narrow in nature and deficient in resources, which are scarce and expensive. Recently, the synthesis of metabolites in the heterologous host has opened up the potential for large-scale and sustainable production of crocins, especially for the main active compounds crocin I and crocin II. In this study, GjCCD4a, GjALDH2C3, GjUGT74F8, and GjUGT94E13 from G. jasminoides fruits were expressed in Nicotiana benthamiana. The highest total content of crocins in T1 generation tobacco can reach 78,362 ng/g FW (fresh weight) and the dry weight is expected to reach 1,058,945 ng/g DW (dry weight). Surprisingly, the primary effective constituents crocin I and crocin II can account for 99% of the total crocins in transgenic plants. The strategy mentioned here provides an alternative platform for the scale-up production of crocin I and crocin II in tobacco. Full article

(This article belongs to the Special Issue Biosynthesis and Regulatory Mechanism of Secondary Metabolites in Medicinal Plants)

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Open AccessArticle

Characterization of Volatile Organic Compounds in Five Celery (Apium graveolens L.) Cultivars with Different Petiole Colors by HS-SPME-GC-MS

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Int. J. Mol. Sci. 2023, 24(17), 13343; https://doi.org/10.3390/ijms241713343 - 28 Aug 2023

Viewed by 289

Abstract

Celery (Apium graveolens L.) is an important vegetable crop cultivated worldwide for its medicinal properties and distinctive flavor. Volatile organic compound (VOC) analysis is a valuable tool for the identification and classification of species. Currently, less research has been conducted on aroma compounds in different celery varieties and colors. In this study, five different colored celery were quantitatively analyzed for VOCs using HS-SPME, GC-MS determination, and stoichiometry methods. The result revealed that γ-terpinene, d-limonene, 2-hexenal,-(E)-, and β-myrcene contributed primarily to the celery aroma. The composition of compounds in celery exhibited a correlation not only with the color of the variety, with green celery displaying a higher concentration compared with other varieties, but also with the specific organ, whereby the content and distribution of volatile compounds were primarily influenced by the leaf rather than the petiole. Seven key genes influencing terpenoid synthesis were screened to detect expression levels. Most of the genes exhibited higher expression in leaves than petioles. In addition, some genes, particularly AgDXS and AgIDI, have higher expression levels in celery than other genes, thereby influencing the regulation of terpenoid synthesis through the MEP and MVA pathways, such as hydrocarbon monoterpenes. This study identified the characteristics of flavor compounds and key aroma components in different colored celery varieties and explored key genes involved in the regulation of terpenoid synthesis, laying a theoretical foundation for understanding flavor chemistry and improving its quality. Full article

(This article belongs to the Special Issue Biosynthesis and Regulatory Mechanism of Secondary Metabolites in Medicinal Plants)

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Open AccessArticle

Biosynthesis of α-Bisabolol by Farnesyl Diphosphate Synthase and α-Bisabolol Synthase and Their Related Transcription Factors in Matricaria recutita L.

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Int. J. Mol. Sci. 2023, 24(2), 1730; https://doi.org/10.3390/ijms24021730 - 15 Jan 2023

Cited by 2 | Viewed by 1525

Abstract

The essential oil of German chamomile (Matricaria recutita L.) is widely used in food, cosmetics, and the pharmaceutical industry. α-Bisabolol is the main active substance in German chamomile. Farnesyl diphosphate synthase (FPS) and α-bisabolol synthase (BBS) are key enzymes related to the α-bisabolol biosynthesis pathway. However, little is known about the α-bisabolol biosynthesis pathway in German chamomile, especially the transcription factors (TFs) related to the regulation of α-bisabolol synthesis. In this study, we identified MrFPS and MrBBS and investigated their functions by prokaryotic expression and expression in hairy root cells of German chamomile. The results suggest that MrFPS is the key enzyme in the production of sesquiterpenoids, and MrBBS catalyzes the reaction that produces α-bisabolol. Subcellular localization analysis showed that both MrFPS and MrBBS proteins were located in the cytosol. The expression levels of both MrFPS and MrBBS were highest in the extension period of ray florets. Furthermore, we cloned and analyzed the promoters of MrFPS and MrBBS. A large number of cis-acting elements related to light responsiveness, hormone response elements, and cis-regulatory elements that serve as putative binding sites for specific TFs in response to various biotic and abiotic stresses were identified. We identified and studied TFs related to MrFPS and MrBBS, including WRKY, AP2, and MYB. Our findings reveal the biosynthesis and regulation of α-bisabolol in German chamomile and provide novel insights for the production of α-bisabolol using synthetic biology methods. Full article

(This article belongs to the Special Issue Biosynthesis and Regulatory Mechanism of Secondary Metabolites in Medicinal Plants)

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Open AccessArticle

A Novel R2R3-MYB Transcription Factor SbMYB12 Positively Regulates Baicalin Biosynthesis in Scutellaria baicalensis Georgi

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Int. J. Mol. Sci. 2022, 23(24), 15452; https://doi.org/10.3390/ijms232415452 - 07 Dec 2022

Cited by 5 | Viewed by 879

Abstract

Scutellaria baicalensis Georgi is an annual herb from the Scutellaria genus that has been extensively used as a traditional medicine for over 2000 years in China. Baicalin and other flavonoids have been identified as the principal bioactive ingredients. The biosynthetic pathway of baicalin in S. baicalensis has been elucidated; however, the specific functions of R2R3-MYB TF, which regulates baicalin synthesis, has not been well characterized in S. baicalensis to date. Here, a S20 R2R3-MYB TF (SbMYB12), which encodes 263 amino acids with a length of 792 bp, was expressed in all tested tissues (mainly in leaves) and responded to exogenous hormone methyl jasmonate (MeJA) treatment. The overexpression of SbMYB12 significantly promoted the accumulation of flavonoids such as baicalin and wogonoside in S. baicalensis hairy roots. Furthermore, biochemical experiments revealed that SbMYB12 is a nuclear-localized transcription activator that binds to the SbCCL7-4, SbCHI-2, and SbF6H-1 promoters to activate their expression. These results illustrate that SbMYB12 positively regulates the generation of baicalin and wogonoside. In summary, this work revealed a novel S20 R2R3-MYB regulator and enhances our understanding of the transcriptional and regulatory mechanisms of baicalin biosynthesis, as well as sheds new light on metabolic engineering in S. baicalensis. Full article

(This article belongs to the Special Issue Biosynthesis and Regulatory Mechanism of Secondary Metabolites in Medicinal Plants)

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Open AccessArticle

Transcription Factor SmSPL2 Inhibits the Accumulation of Salvianolic Acid B and Influences Root Architecture

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Int. J. Mol. Sci. 2022, 23(21), 13549; https://doi.org/10.3390/ijms232113549 - 04 Nov 2022

Viewed by 769

Abstract

The SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE (SPL) transcription factor play vital roles in plant growth and development. Although 15 SPL family genes have been recognized in the model medical plant Salvia miltiorrhiza Bunge, most of them have not been functionally characterized to date. Here, we performed a careful characterization of SmSPL2, which was expressed in almost all tissues of S. miltiorrhiza and had the highest transcriptional level in the calyx. Meanwhile, SmSPL2 has strong transcriptional activation activity and resides in the nucleus. We obtained overexpression lines of SmSPL2 and rSmSPL2 (miR156-resistant SmSPL2). Morphological changes in roots, including longer length, fewer adventitious roots, decreased lateral root density, and increased fresh weight, were observed in all of these transgenic lines. Two rSmSPL2-overexpressed lines were subjected to transcriptome analysis. Overexpression of rSmSPL2 changed root architectures by inhibiting biosynthesis and signal transduction of auxin, while triggering that of cytokinin. The salvianolic acid B (SalB) concentration was significantly decreased in rSmSPL2-overexpressed lines. Further analysis revealed that SmSPL2 binds directly to the promoters of Sm4CL9, SmTAT1, and SmPAL1 and inhibits their expression. In conclusion, SmSPL2 is a potential gene that efficiently manipulate both root architecture and SalB concentration in S. miltiorrhiza. Full article

(This article belongs to the Special Issue Biosynthesis and Regulatory Mechanism of Secondary Metabolites in Medicinal Plants)

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Open AccessArticle

Integrating Metabolomics and Transcriptomics to Unveil Atisine Biosynthesis in Aconitum gymnandrum Maxim

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Int. J. Mol. Sci. 2022, 23(21), 13463; https://doi.org/10.3390/ijms232113463 - 03 Nov 2022

Cited by 1 | Viewed by 1157

Abstract

Diterpene alkaloids (DAs) are characteristic compounds in Aconitum, which are classified into four skeletal types: C₁₈, C₁₉, C₂₀, and bisditerpenoid alkaloids. C₂₀-DAs are thought to be the precursor of the other types. Their biosynthetic pathway, however, is largely unclear. Herein, we combine metabolomics and transcriptomics to unveil the methyl jasmonate (MJ) inducible biosynthesis of DAs in the sterile seedling of A. gymnandrum, the only species in the Subgenus Gymnaconitum (Stapf) Rapaics. Target metabolomics based on root and aerial portions identified 51 C₁₉-DAs and 15 C₂₀-DAs, with 40 inducible compounds. The highest content of C₂₀-DA atisine was selected for further network analysis. PacBio Isoform sequencing integrated with RNA sequencing not only provided the full-length transcriptome but also their response to induction, revealing 1994 genes that exhibited up-regulated expression. Further, 38 genes involved in terpenoid biosynthesis were identified, including 7 diterpene synthases. In addition to the expected function of the four diterpene synthases, AgCPS5 was identified to be a new ent-8,13-CPP synthase in Aconitum and could also combine with AgKSL1 to form the C₂₀-DAs precursor ent-atiserene. Combined with multiple network analyses, six CYP450 and seven 2-ODD genes predicted to be involved in the biosynthesis of atisine were also identified. This study not only sheds light on diterpene synthase evolution in Aconitum but also provides a rich dataset of full-length transcriptomes, systemic metabolomes, and gene expression profiles, setting the groundwork for further investigation of the C₂₀-DAs biosynthesis pathway. Full article

(This article belongs to the Special Issue Biosynthesis and Regulatory Mechanism of Secondary Metabolites in Medicinal Plants)

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Open AccessArticle

Plant Metabolic Engineering by Multigene Stacking: Synthesis of Diverse Mogrosides

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Int. J. Mol. Sci. 2022, 23(18), 10422; https://doi.org/10.3390/ijms231810422 - 09 Sep 2022

Cited by 3 | Viewed by 1668

Abstract

Mogrosides are a group of health-promoting natural products that extracted from Siraitia grosvenorii fruit (Luo-han-guo or monk fruit), which exhibited a promising practical application in natural sweeteners and pharmaceutical development. However, the production of mogrosides is inadequate to meet the need worldwide, and uneconomical synthetic chemistry methods are not generally recommended for structural complexity. To address this issue, an in-fusion based gene stacking strategy (IGS) for multigene stacking has been developed to assemble 6 mogrosides synthase genes in pCAMBIA1300. Metabolic engineering of Nicotiana benthamiana and Arabidopsis thaliana to produce mogrosides from 2,3-oxidosqualene was carried out. Moreover, a validated HPLC-MS/MS method was used for the quantitative analysis of mogrosides in transgenic plants. Herein, engineered Arabidopsis thaliana produced siamenoside I ranging from 29.65 to 1036.96 ng/g FW, and the content of mogroside III at 202.75 ng/g FW, respectively. The production of mogroside III was from 148.30 to 252.73 ng/g FW, and mogroside II-E with concentration between 339.27 and 5663.55 ng/g FW in the engineered tobacco, respectively. This study provides information potentially applicable to develop a powerful and green toolkit for the production of mogrosides. Full article

(This article belongs to the Special Issue Biosynthesis and Regulatory Mechanism of Secondary Metabolites in Medicinal Plants)

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