Transcriptomic Analysis Reveals the Mechanism of Glycyrrhizic acid Biosynthesis in Glycyrrhiza Uralensis Fisch.

Abstract In order to better understand the mechanism of glycyrrhizic acid biosynthesis and explore important enzyme gene resources in Glycyrrhiza uralensis Fisch., we sequenced the transcriptome of the adventitious roots of G. uralensis treated by methyl jasmonate (MJ) and assembled the de novo sequence. 256503 unique transcripts with an average length of 898bp were produced. Transcriptome sequencing and data analysis showed that the key genes of glycyrrhizic acid biosynthesis changed significantly after MJ treatment. 2720 up-regulated genes and 3493 down regulated genes were found. In the process of oxidation and glycosylation of glycyrrhizic acid biosynthesis. A putative CYP450 gene (Cluster-30944.70498) is positively correlated with glycyrrhetinic acid. The glycosyltransferase gene (Cluster-30944.25725) is positively correlated with glycyrrhizic acid and glycyrrhetinic acid. In addition, we found an AP2-EREBP family transcription factor (Cluster-30944.55070). It had high amino acid sequence similarity with PgERF1. In Panax ginseng, PgERF1 was identified as promoting the biosynthesis of triterpenoid saponins. According to the correlation analysis of transcription factors, functional gene expression and component accumulation, we speculated that this transcription factor can positively regulate the expression of farnesyl diphosphate, squalene epoxide and glycosyltransferase (Cluster-30944.25725) genes and ultimately increase the content of glycyrrhizic acid.

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GuUGT, a glycosyltransferase from Glycyrrhiza uralensis , exhibits glycyrrhetinic acid 3- and 30-O-glycosylation

Royal Society Open Science ◽

10.1098/rsos.191121 ◽

2019 ◽

Vol 6 (10) ◽

pp. 191121 ◽

Cited By ~ 1

Author(s):

Ying Huang ◽

Da Li ◽

Jinhe Wang ◽

Yi Cai ◽

Zhubo Dai ◽

...

Keyword(s):

Biosynthetic Pathway ◽

Glycyrrhetinic Acid ◽

Glycyrrhiza Uralensis ◽

Transcriptome Data ◽

Bioactive Components ◽

Triterpenoid Saponins ◽

Genes Encoding ◽

Engineered Yeast ◽

Biochemical Analyses

Glycyrrhiza uralensis is a well-known herbal medicine that contains triterpenoid saponins as the predominant bioactive components, and these compounds include glycyrrhetinic acid (GA)-glycoside derivatives. Although two genes encoding UDP-glycosyltransferases (UGTs) that glycosylate these derivates have been functionally characterized in G. uralensis , the mechanisms of glycosylation by other UGTs remain unknown. Based on the available transcriptome data, we isolated a UGT with expression in the roots of G. uralensis . This UGT gene possibly encodes a glucosyltransferase that glycosylates GA derivatives at the 3-OH site. Biochemical analyses revealed that the recombinant UGT enzyme could transfer a glucosyl moiety to the free 3-OH or 30-COOH groups of GA. Furthermore, engineered yeast harbouring genes involved in the biosynthetic pathway for GA-glycoside derivates produced GA-3- O -β-D-glucoside, implying that the enzyme has GA 3-O-glucosyltransferase activity in vivo . Our results could provide a frame for understand the function of the UGT gene family, and also is important for further studies of triterpenoids biosynthesis in G. uralensis .

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LSP1, a responsive protein from Meyerozyma guilliermondii , elicits defence response and improves glycyrrhizic acid biosynthesis in Glycyrrhiza uralensis Fisch adventitious roots

Journal of Cellular Physiology ◽

10.1002/jcp.25811 ◽

2017 ◽

Vol 232 (12) ◽

pp. 3510-3519 ◽

Cited By ~ 1

Author(s):

Juan Wang ◽

Jianli Li ◽

Jing Li ◽

Jinxin Li ◽

Shujie Liu ◽

...

Keyword(s):

Adventitious Roots ◽

Glycyrrhizic Acid ◽

Defence Response ◽

Glycyrrhiza Uralensis ◽

Acid Biosynthesis ◽

Meyerozyma Guilliermondii ◽

Glycyrrhiza Uralensis Fisch

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Cloning and Characterization of Two cDNA Sequences Coding Squalene Synthase Involved in Glycyrrhizic Acid Biosynthesis in Glycyrrhiza uralensis

Lecture Notes in Electrical Engineering - Frontier and Future Development of Information Technology in Medicine and Education ◽

10.1007/978-94-007-7618-0_32 ◽

2013 ◽

pp. 329-342 ◽

Cited By ~ 4

Author(s):

Ying Liu ◽

Ning Zhang ◽

Honghao Chen ◽

Ya Gao ◽

Hao Wen ◽

...

Keyword(s):

Glycyrrhizic Acid ◽

Squalene Synthase ◽

Glycyrrhiza Uralensis ◽

Acid Biosynthesis ◽

Cdna Sequences

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A tuber mustard AP2/ERF transcription factor gene, BjABR1, functioning in abscisic acid and abiotic stress responses, and evolutionary trajectory of the ABR1 homologous genes in Brassica species

PeerJ ◽

10.7717/peerj.6071 ◽

2018 ◽

Vol 6 ◽

pp. e6071 ◽

Cited By ~ 5

Author(s):

Liuxin Xiang ◽

Chao Liu ◽

Jingzhi Luo ◽

Lin He ◽

Yushan Deng ◽

...

Keyword(s):

Transcription Factor ◽

Abscisic Acid ◽

Abiotic Stress ◽

Stress Responses ◽

Sequence Similarity ◽

Amino Acid Sequence Similarity ◽

Genome Database ◽

Homologous Genes ◽

High Amino Acid ◽

Tuber Mustard

The AP2/ERF superfamily of transcription factors is one of the largest transcription factor families in plants and plays an important role in plant development processes and stress responses. In this study, BjABR1, an AP2/ERF superfamily gene, from tuber mustard (Brassica juncea var. tumida Tsen et Lee), sharing high amino acid sequence similarity with the AtABR1 (Arabidopsis thaliana AP2-like abscisic acid repressor 1) gene, were performed functional research, and the ABR1 homologous genes in Brassica species were identified and performed phylogenetic analysis. The promoter sequence of BjABR1 contained many phytohormone- and stress-related cis-elements; ABA (abscisic acid) and abiotic stresses can induce BjABR1 expression in tuber mustard; overexpression of BjABR1 in Arabidopsis can alleviate plant sensitivity to ABA and salt and osmotic stresses, and the alleviation may be due to changes in stress/ABA-induced gene expression. These results indicated that BjABR1 functions in ABA and abiotic stress responses. By BLAST searches against the genome database of five Brassica species (three diploids, B. rapa, B. nigra, and B. oleracea, and two allotetraploid, B. juncea and B. napus) using the protein sequence of AtABR1, 3, 3, 3, 6, and 5 ABR1 homologous genes in B. nigra, B. rapa, B. oleracea, B. juncea, and B. napus were identified, respectively, and they shared high sequence similarity. By sequence analysis, annotation mistakes of the protein-coding regions of two ABR1 homologous genes, GSBRNA2T00134741001 and BjuB007684, were found and corrected. Then, the evolution analysis of these ABR1 homologous genes showed that the ancestor of the three diploid species had three ABR1 homologous genes and each diploid inherited all the three genes from their ancestor; then, allotetraploid B. juncea inherited all the six genes from B. rapa and B. nigra with no gene lost, while allotetraploid B. napus inherited all the three genes from B. oleracea and two genes from B. rapa with one gene lost, indicating that ABR1 homologous genes possessed greater hereditary conservation in Brassica species. The ABR1 homologous genes between B. rapa and B. oleracea shared much higher sequence similarity compared to that of B. nigra in diploid species, indicating that ABR1 homologous genes in B. nigra had experienced more rapid evolution, and B. rapa and B. oleracea may share closer relationship compared to B. nigra. Moreover, the spatial and temporal expression analysis of six ABR1 homologous genes of tuber mustard showed that they possessed different expression models. These results imply that ABR1 homologous genes are important to Brassica plants, and they may possess similar function in ABA and abiotic stress responses but play a role in different tissues and growing stages of plant. This study will provide the foundation to the functional research of ABR1 homologous genes in the Brassica species and help to reveal and understand the evolution mechanisms of Brassica species.

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Botcinic acid biosynthesis in Botrytis cinerea relies on a subtelomeric gene cluster surrounded by relics of transposons and is regulated by the Zn2Cys6 transcription factor BcBoa13

Current Genetics ◽

10.1007/s00294-019-00952-4 ◽

2019 ◽

Vol 65 (4) ◽

pp. 965-980 ◽

Cited By ~ 9

Author(s):

Antoine Porquier ◽

Javier Moraga ◽

Guillaume Morgant ◽

Bérengère Dalmais ◽

Adeline Simon ◽

...

Keyword(s):

Transcription Factor ◽

Botrytis Cinerea ◽

Gene Cluster ◽

Acid Biosynthesis

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Functional and evolutionary characterization of a secondary metabolite gene cluster in budding yeasts

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1806268115 ◽

2018 ◽

Vol 115 (43) ◽

pp. 11030-11035 ◽

Cited By ~ 33

Author(s):

David J. Krause ◽

Jacek Kominek ◽

Dana A. Opulente ◽

Xing-Xing Shen ◽

Xiaofan Zhou ◽

...

Keyword(s):

Transcription Factor ◽

Gene Cluster ◽

Kluyveromyces Lactis ◽

Phylogenetic Analyses ◽

Iron Binding ◽

Acid Biosynthesis ◽

Transcription Factor Genes ◽

Domains Of Life ◽

Secondary Metabolite Gene Cluster

Secondary metabolites are key in how organisms from all domains of life interact with their environment and each other. The iron-binding molecule pulcherrimin was described a century ago, but the genes responsible for its production in budding yeasts have remained uncharacterized. Here, we used phylogenomic footprinting on 90 genomes across the budding yeast subphylum Saccharomycotina to identify the gene cluster associated with pulcherrimin production. Using targeted gene replacements in Kluyveromyces lactis, we characterized the four genes that make up the cluster, which likely encode two pulcherriminic acid biosynthesis enzymes, a pulcherrimin transporter, and a transcription factor involved in both biosynthesis and transport. The requirement of a functional putative transporter to utilize extracellular pulcherrimin-complexed iron demonstrates that pulcherriminic acid is a siderophore, a chelator that binds iron outside the cell for subsequent uptake. Surprisingly, we identified homologs of the putative transporter and transcription factor genes in multiple yeast genera that lacked the biosynthesis genes and could not make pulcherrimin, including the model yeast Saccharomyces cerevisiae. We deleted these previously uncharacterized genes and showed they are also required for pulcherrimin utilization in S. cerevisiae, raising the possibility that other genes of unknown function are linked to secondary metabolism. Phylogenetic analyses of this gene cluster suggest that pulcherrimin biosynthesis and utilization were ancestral to budding yeasts, but the biosynthesis genes and, subsequently, the utilization genes, were lost in many lineages, mirroring other microbial public goods systems that lead to the rise of cheater organisms.

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The Drosophila homeobox gene optix is capable of inducing ectopic eyes by an eyeless-independent mechanism

Development ◽

10.1242/dev.127.9.1879 ◽

2000 ◽

Vol 127 (9) ◽

pp. 1879-1886 ◽

Cited By ~ 7

Author(s):

M. Seimiya ◽

W.J. Gehring

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Gene Family ◽

Eye Development ◽

Ectopic Expression ◽

Amino Acid Sequence Similarity ◽

Sine Oculis ◽

High Amino Acid ◽

Independent Mechanism ◽

Ectopic Eyes

optix is a new member of the Six/so gene family from Drosophila that contains both a six domain and a homeodomain. Because of its high amino acid sequence similarity with the mouse Six3 gene, optix is considered to be the orthologous gene from Drosophila rather than sine oculis, as previously believed. optix expression was detected in the eye, wing and haltere imaginal discs. Ectopic expression of optix leads to the formation of ectopic eyes suggesting that optix has important functions in eye development. Although optix and sine oculis belong to the same gene family (Six/so) and share a high degree of amino acid sequence identity, there are a number of factors which suggest that their developmental roles are different: (1) the expression patterns of optix and sine oculis are clearly distinct; (2) sine oculis acts downstream of eyeless, whereas optix is expressed independently of eyeless; (3) sine oculis functions synergistically with eyes absent in eye development whereas optix does not; (4) ectopic expression of optix alone, but not of sine oculis can induce ectopic eyes in the antennal disc. These results suggest that optix is involved in eye morphogenesis by an eyeless-independent mechanism.

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Glycyrrhizic Acid for COVID-19: Findings of Targeting Pivotal Inflammatory Pathways Triggered by SARS-CoV-2

Frontiers in Pharmacology ◽

10.3389/fphar.2021.631206 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wenjiang Zheng ◽

Xiufang Huang ◽

Yanni Lai ◽

Xiaohong Liu ◽

Yong Jiang ◽

...

Keyword(s):

Transcription Factor ◽

Protein Interactions ◽

Glycyrrhizic Acid ◽

Enrichment Analysis ◽

Host Factors ◽

Pathway Enrichment Analysis ◽

Protein Protein Interactions ◽

Health Crisis ◽

Inflammatory Pathways ◽

Anti Inflammatory

Background: Coronavirus disease 2019 (COVID-19) is now a worldwide public health crisis. The causative pathogen is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Novel therapeutic agents are desperately needed. Because of the frequent mutations in the virus and its ability to cause cytokine storms, targeting the viral proteins has some drawbacks. Targeting cellular factors or pivotal inflammatory pathways triggered by SARS-CoV-2 may produce a broader range of therapies. Glycyrrhizic acid (GA) might be beneficial against SARS-CoV-2 because of its anti-inflammatory and antiviral characteristics and possible ability to regulate crucial host factors. However, the mechanism underlying how GA regulates host factors remains to be determined.Methods: In our report, we conducted a bioinformatics analysis to identify possible GA targets, biological functions, protein-protein interactions, transcription-factor-gene interactions, transcription-factor-miRNA coregulatory networks, and the signaling pathways of GA against COVID-19.Results: Protein-protein interactions and network analysis showed that ICAM1, MMP9, TLR2, and SOCS3 had higher degree values, which may be key targets of GA for COVID-19. GO analysis indicated that the response to reactive oxygen species was significantly enriched. Pathway enrichment analysis showed that the IL-17, IL-6, TNF-α, IFN signals, complement system, and growth factor receptor signaling are the main pathways. The interactions of TF genes and miRNA with common targets and the activity of TFs were also recognized.Conclusions: GA may inhibit COVID-19 through its anti-oxidant, anti-viral, and anti-inflammatory effects, and its ability to activate the immune system, and targeted therapy for those pathways is a predominant strategy to inhibit the cytokine storms triggered by SARS-CoV-2 infection.

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