scholarly journals Endophytic fungus Pseudodidymocyrtis lobariellae KL27 promotes taxol biosynthesis and accumulation in Taxus chinensis

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiaoying Cao ◽  
Lingxia Xu ◽  
Jingyi Wang ◽  
Mengmeng Dong ◽  
Chunyan Xu ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Endophytic Fungus ◽  
Fermentation Broth ◽  
Early Stage ◽  
Fold Increase ◽  
Taxus Chinensis ◽  
Biosynthesis Pathway ◽  
Taxol Biosynthesis ◽  
Key Genes ◽  
Differential Expressed Genes

Abstract Background Taxol from Taxus species is a precious drug used for the treatment of cancer and can effectively inhibit the proliferation of cancer cells. However, the growth of Taxus plants is very slow and the content of taxol is quite low. Therefore, it is of great significance to improve the yield of taxol by modern biotechnology without destroying the wild forest resources. Endophytic fungus which symbiosis with their host plants can promote the growth and secondary metabolism of medicinal plants. Results Here, an endophytic fungus KL27 was isolated from T. chinensis, and identified as Pseudodidymocyrtis lobariellae. The fermentation broth of KL27 (KL27-FB) could significantly promote the accumulation of taxol in needles of T. chinensis, reaching 0.361 ± 0.082 mg/g·DW (dry weight) at 7 days after KL27-FB treatment, which is 3.26-fold increase as compared to the control. The RNA-seq and qRT-PCR showed that KL27-FB could significantly increase the expression of key genes involved in the upstream pathway of terpene synthesis (such as DXS and DXR) and those in the taxol biosynthesis pathway (such as GGPPS, TS, T5OH, TAT, T10OH, T14OH, T2OH, TBT, DBAT and PAM), especially at the early stage of the stimulation. Moreover, the activation of jasmonic acid (JA) biosynthesis and JA signal transduction, and its crosstalk with other hormones, such as gibberellin acid (GA), ethylene (ET) and salicylic acid (SA), explained the elevation of most of the differential expressed genes related to taxol biosynthesis pathway. Moreover, TF (transcriptional factor)-encoding genes, including MYBs, ethylene-responsive transcription factors (ERFs) and basic/helix-loop-helix (bHLH), were detected as differential expressed genes after KL27-FB treatment, further suggested that the regulation of hormone signaling on genes of taxol biosynthesis was mediated by TFs. Conclusions Our results indicated that fermentation broth of endophytic fungus KL27-FB could effectively enhance the accumulation of taxol in T. chinensis needles by regulating the phytohormone metabolism and signal transduction and further up-regulating the expression of multiple key genes involved in taxol biosynthesis. This study provides new insight into the regulatory mechanism of how endophytic fungus promotes the production and accumulation of taxol in Taxus sp.

scholarly journals Omic analysis of the endangered Taxaceae species Pseudotaxus chienii revealed the differences in taxol biosynthesis pathway between Pseudotaxus and Taxus yunnanensis trees

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chunna Yu ◽  
Chengchao Zhang ◽  
Xinyun Xu ◽  
Jiefang Huang ◽  
Yueyue Chen ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Large Scale ◽  
Biosynthesis Pathway ◽  
High Accumulation ◽  
Taxol Biosynthesis ◽  
Taxus Yunnanensis ◽  
Primary And Secondary Metabolism ◽  
Key Genes ◽  
Differential Expressed Genes ◽  
Large Scale Cultivation

Abstract Background Taxol is an efficient anticancer drug accumulated in Taxus species. Pseudotaxus chienii is an important member of Taxaceae, however, the level of six taxoids in P. chienii is largely unknown. Results High accumulation of 10-DAB, taxol, and 7-E-PTX suggested that P. chienii is a good taxol-yielding species for large-scale cultivation. By the omics approaches, a total of 3,387 metabolites and 61,146 unigenes were detected and annotated. Compared with a representative Taxus tree (Taxus yunnanensis), most of the differentially accumulated metabolites and differential expressed genes were assigned into 10 primary and secondary metabolism pathways. Comparative analyses revealed the variations in the precursors and intermediate products of taxol biosynthesis between P. chienii and T. yunnanensis. Taxusin-like metabolites highly accumulated in P. chienii, suggesting a wider value of P. chienii in pharmaceutical industry. Conclusions In our study, the occurrence of taxoids in P. chienii was determined. The differential expression of key genes involved in the taxol biosynthesis pathway is the major cause of the differential accumulation of taxoids. Moreover, identification of a number of differentially expressed transcription factors provided more candidate regulators of taxol biosynthesis. Our study may help to reveal the differences between Pseudotaxus and Taxus trees, and promote resource utilization of the endangered and rarely studied P. chienii.

Hydrogen Peroxide from the Oxidative Burst is Not Involved in the Induction of Taxol Biosynthesis in Taxus chinensis Cells

2003 ◽  
Vol 58 (7-8) ◽  
pp. 605-608 ◽  
Author(s):  
Wen Zhi Lan ◽  
Wen Min Qin ◽  
Long Jiang Yu ◽  
Xi Yang
Keyword(s):  
Hydrogen Peroxide ◽  
Ascorbic Acid ◽  
Superoxide Dismutase ◽  
Cell Suspension Cultures ◽  
Fold Increase ◽  
Fungal Elicitor ◽  
Taxus Chinensis ◽  
Taxol Biosynthesis ◽  
Diphenylene Iodonium ◽  
Taxol Production

Abstract In cell suspension cultures of Taxus chinensis, 40 mg/l fungal elicitor from Aspergillus niger and 20 μm HgCl2 elicited 5.7 and 3.6 mg/l taxol, which was a 9-fold and 5- fold increase vs. compared with the control, respectively. The fungal elicitor induced hydrogen peroxide (H2O2) accumulation but HgCl2 did not, indicating that H2O2 was not necessary for enhancement of taxol induced by elicitor. Compared with the treatment with fungal elicitor alone, exogenous catalase, ascorbic acid, diphenylene iodonium and superoxide dismutase induced a 0.45, 0.4, 0.7 and 1.4-fold H2O2, but elicited taxol production, which was 0.98, 1.2, 1.1 and 0.9-fold, respectively, vs. non-treated cells. Elicitor-induced taxol production was not accorded with the amount of H2O2 production.

scholarly journals Systematical Engineering of Synthetic Yeast for Enhanced Production of Lycopene

2021 ◽  
Vol 8 (1) ◽  
pp. 14
Author(s):  
Yu Zhang ◽  
Tsan-Yu Chiu ◽  
Jin-Tao Zhang ◽  
Shu-Jie Wang ◽  
Shu-Wen Wang ◽  
...  
Keyword(s):  
Copy Number ◽  
Chromosome Rearrangement ◽  
Fold Increase ◽  
Host Strain ◽  
Target Product ◽  
Biosynthesis Pathway ◽  
Suitable Host ◽  
Enhanced Production ◽  
Condition Optimization ◽  
Heterologous Pathway

Synthetic biology allows the re-engineering of biological systems and promotes the development of bioengineering to a whole new level, showing great potential in biomanufacturing. Here, in order to make the heterologous lycopene biosynthesis pathway compatible with the host strain YSy 200, we evolved YSy200 using a unique Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) system that is built in the Sc2.0 synthetic yeast. By inducing SCRaMbLE, we successfully identified a host strain YSy201 that can be served as a suitable host to maintain the heterologous lycopene biosynthesis pathway. Then, we optimized the lycopene biosynthesis pathway and further integrated into the rDNA arrays of YSy201 to increase its copy number. In combination with culturing condition optimization, we successfully screened out the final yeast strain YSy222, which showed a 129.5-fold increase of lycopene yield in comparison with its parental strain. Our work shows that, the strategy of combining the engineering efforts on both the lycopene biosynthesis pathway and the host strain can improve the compatibility between the heterologous pathway and the host strain, which can further effectively increase the yield of the target product.

scholarly journals FGF23, a novel muscle biomarker detected in the early stages of ALS

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ying Si ◽  
Mohamed Kazamel ◽  
Michael Benatar ◽  
Joanne Wuu ◽  
Yuri Kwon ◽  
...  
Keyword(s):  
Biomarker Discovery ◽  
Clinical Symptoms ◽  
Early Stage ◽  
Fold Increase ◽  
Progressive Increase ◽  
Molecular Signature ◽  
Muscle Membrane ◽  
Sequencing Project ◽  
Progressive Muscle Weakness ◽  
End Stage

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Skeletal muscle is a prime source for biomarker discovery since it is one of the earliest sites to manifest disease pathology. From a prior RNA sequencing project, we identified FGF23 as a potential muscle biomarker in ALS. Here, we validate this finding with a large collection of ALS muscle samples and found a 13-fold increase over normal controls. FGF23 was also increased in the SOD1G93A mouse, beginning at a very early stage and well before the onset of clinical symptoms. FGF23 levels progressively increased through end-stage in the mouse. Immunohistochemistry of ALS muscle showed prominent FGF23 immunoreactivity in the endomysial connective tissue and along the muscle membrane and was significantly higher around grouped atrophic fibers compared to non-atrophic fibers. ELISA of plasma samples from the SOD1G93A mouse showed an increase in FGF23 at end-stage whereas no increase was detected in a large cohort of ALS patients. In conclusion, FGF23 is a novel muscle biomarker in ALS and joins a molecular signature that emerges in very early preclinical stages. The early appearance of FGF23 and its progressive increase with disease progression offers a new direction for exploring the molecular basis and response to the underlying pathology of ALS.

scholarly journals Enhanced 2,5-furandicarboxylic acid (FDCA) production in RaoultellaornithinolyticaBF60 by manipulation of the key genes in FDCA biosynthesis pathway

2018 ◽  
Vol 28 (12) ◽  
pp. 1999-2008 ◽  
Author(s):  
Haibo Yuan ◽  
Yanfeng Liu ◽  
Xueqin Lv ◽  
Jianghua Li ◽  
Guocheng Du ◽  
...  
Keyword(s):  
Biosynthesis Pathway ◽  
Key Genes ◽  
Furandicarboxylic Acid

Abstract 4579: Endogenous Brain Natriuretic Peptide (BNP) Protects Against Apoptosis of Ischemic Human Astrocytes in an Autocrine Fashion

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Chisato Katoh ◽  
Hirofumi Tomita ◽  
Norifumi Metoki ◽  
Genta Saitoh ◽  
Tomohiro Osanai ◽  
...  
Keyword(s):  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Early Stage ◽  
Infarct Volume ◽  
Fold Increase ◽  
Brain Diseases ◽  
Loss Of Function ◽  
Human Astrocytes ◽  
Apoptotic Effect ◽  
And Function

The plasma brain natriuretic peptide (BNP) level is increased in the acute phase of human stroke, but its source and function are unclear. Recently, we showed that the BNP level was higher in atherothrombotic cerebral infarction (69.1±9.4 pg/ml) than in control subjects (31.1±5.4 pg/ml), and that the BNP level in ischemic stroke was positively correlated with the NIH Stroke Scale (r=0.41, p<0.05) and infarct volume (r=0.34, p<0.05). Astrocytes provide metabolic and trophic support to neurons and modulate synaptic activities. At the early stage of brain ischemia, astrocytes are swollen, and their damage may compromise postischemic neuronal survival. We tested the hypothesis that human astrocytes produce BNP under hypoxia, and this endogenous BNP protects against apoptosis in an autocrine fashion. The human astrocyte cell line, U373MG, was exposed to hypoxia (O 2 ≤1%) for 24 hours. The ratio of BNP to GAPDH mRNA was increased by 7.7±.0 fold after 12-hour hypoxia and further increased by 8.6±1.6 fold after 24-hour hypoxia compared with that in 3-hour normoxia (both, p<0.01). The protein expression assessed by Western blot was increased by 2.0±0.4 fold at 24 hours (n=5, p<0.05). Tyrosine phosphorylation of c-Src was observed by 2.0±0.2-fold increase at 30 minutes. These responses to hypoxia were all blocked by pretreatment with PP1 at 50μM, an inhibitor of c-Src. Apoptosis was measured by detecting caspase activation by flow cytometry, and it was increased by 2.5±0.1 fold after 24-hour hypoxia compared with that in normoxia. To investigate the role of up-regulated BNP in apoptosis, we performed the loss of function test by transfecting a specific siRNA for NPPB that suppressed BNP by more than 80%. The activity of caspases in the BNP knockdown cells was increased by 3.2±0.2 fold after 24-hour hypoxia compared with that in normoxia (n=5, p<0.001), and it was greater than that in the cells transfected with non-targeting siRNA. These results indicate that hypoxia increases BNP gene expression through the c-Src-dependent signaling cascade in the human astrocytes. Endogenous BNP shows brain protection via the anti-apoptotic effect. BNP may be useful in the treatment of ischemic brain diseases.

scholarly journals Transcriptome Analysis Reveals Key Seed-Development Genes in Common Buckwheat (Fagopyrum esculentum)

2019 ◽  
Vol 20 (17) ◽  
pp. 4303 ◽  
Author(s):  
Hongyou Li ◽  
Qiuyu Lv ◽  
Jiao Deng ◽  
Juan Huang ◽  
Fang Cai ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Seed Development ◽  
Seed Size ◽  
Molecular Mechanisms ◽  
Signal Transduction Pathway ◽  
Fagopyrum Esculentum ◽  
Rna Seq ◽  
Common Buckwheat ◽  
Size Change ◽  
Key Genes

Seed development is an essential and complex process, which is involved in seed size change and various nutrients accumulation, and determines crop yield and quality. Common buckwheat (Fagopyrum esculentum Moench) is a widely cultivated minor crop with excellent economic and nutritional value in temperate zones. However, little is known about the molecular mechanisms of seed development in common buckwheat (Fagopyrum esculentum). In this study, we performed RNA-Seq to investigate the transcriptional dynamics and identify the key genes involved in common buckwheat seed development at three different developmental stages. A total of 4619 differentially expressed genes (DEGs) were identified. Based on the results of Gene Ontology (GO) and KEGG analysis of DEGs, many key genes involved in the seed development, including the Ca2+ signal transduction pathway, the hormone signal transduction pathways, transcription factors (TFs), and starch biosynthesis-related genes, were identified. More importantly, 18 DEGs were identified as the key candidate genes for seed size through homologous query using the known seed size-related genes from different seed plants. Furthermore, 15 DEGs from these identified as the key genes of seed development were selected to confirm the validity of the data by using quantitative real-time PCR (qRT-PCR), and the results show high consistency with the RNA-Seq results. Taken together, our results revealed the underlying molecular mechanisms of common buckwheat seed development and could provide valuable information for further studies, especially for common buckwheat seed improvement.

Two jasmonate-responsive factors, TcERF12 and TcERF15, respectively act as repressor and activator of tasy gene of taxol biosynthesis in Taxus chinensis

2015 ◽  
Vol 89 (4-5) ◽  
pp. 463-473 ◽  
Author(s):  
Meng Zhang ◽  
Shutao Li ◽  
Lin Nie ◽  
Qingpu Chen ◽  
Xiangping Xu ◽  
...  
Keyword(s):  
Taxus Chinensis ◽  
Taxol Biosynthesis

scholarly journals Temporospatial Flavonoids Metabolism Variation in Ginkgo biloba Leaves

2020 ◽  
Vol 11 ◽  
Author(s):  
Ying Guo ◽  
Tongli Wang ◽  
Fang-Fang Fu ◽  
Yousry A. El-Kassaby ◽  
Guibin Wang
Keyword(s):  
Ginkgo Biloba ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Early Stage ◽  
Sunshine Duration ◽  
Flavonoid Biosynthesis ◽  
Flavonoid Glycosides ◽  
Biosynthesis Pathway ◽  
Flavonoids Biosynthesis ◽  
Flavonoid Biosynthesis Pathway

Ginkgo (Ginkgo biloba L.) is a high-value medicinal tree species characterized by its flavonoids beneficial effects that are abundant in leaves. We performed a temporospatial comprehensive transcriptome and metabolome dynamics analyses of clonally propagated Ginkgo plants at four developmental stages (time: May to August) across three different environments (space) to unravel leaves flavonoids biosynthesis variation. Principal component analysis revealed clear gene expression separation across samples from different environments and leaf-developmental stages. We found that flavonoid-related metabolism was more active in the early stage of leaf development, and the content of total flavonoid glycosides and the expression of some genes in flavonoid biosynthesis pathway peaked in May. We also constructed a co-expression regulation network and identified eight GbMYBs and combining with other TF genes (3 GbERFs, 1 GbbHLH, and 1 GbTrihelix) positively regulated the expression of multiple structural genes in the flavonoid biosynthesis pathway. We found that part of these GbTFs (Gb_11316, Gb_32143, and Gb_00128) expressions was negatively correlated with mean minimum temperature and mean relative humidity, while positively correlated with sunshine duration. This study increased our understanding of the molecular mechanisms of flavonoids biosynthesis in Ginkgo leaves and provided insight into the proper production and management of Ginkgo commercial plantations.

scholarly journals Comparative metabolomic analysis reveals the variations in taxoids and flavonoids among three Taxus species

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ting Zhou ◽  
Xiujun Luo ◽  
Chengchao Zhang ◽  
Xinyun Xu ◽  
Chunna Yu ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Side Chain ◽  
Biosynthesis Pathway ◽  
Metabolomic Analysis ◽  
Active Ingredients ◽  
Cancer Treatments ◽  
Taxol Biosynthesis ◽  
Metabolite Pool ◽  
Derivatives Of ◽  
Targeted Approach

Abstract Background Trees of the genus Taxus are highly valuable medicinal plants with multiple pharmacological effects on various cancer treatments. Paclitaxel from Taxus trees is an efficient and widely used anticancer drug, however, the accumulation of taxoids and other active ingredients can vary greatly among Taxus species. In our study, the metabolomes of three Taxus species have been investigated. Results A total of 2246 metabolites assigned to various primary and secondary metabolic pathways were identified using an untargeted approach. Analysis of differentially accumulated metabolites identified 358 T. media-, 220 T. cuspidata-, and 169 T. mairei-specific accumulated metabolites, respectively. By searching the metabolite pool, 7 MEP pathway precursors, 11 intermediates, side chain products and derivatives of paclitaxel, and paclitaxel itself were detected. Most precursors, initiated intermediates were highly accumulated in T. mairei, and most intermediate products approaching the end point of taxol biosynthesis pathway were primarily accumulated in T. cuspidata and T. media. Our data suggested that there were higher-efficiency pathways to paclitaxel in T. cuspidata and T. media compared with in T. mairei. As an important class of active ingredients in Taxus trees, a majority of flavonoids were predominantly accumulated in T. mairei rather than T. media and T. cuspidata. The variations in several selected taxoids and flavonoids were confirmed using a targeted approach. Conclusions Systematic correlativity analysis identifies a number of metabolites associated with paclitaxel biosynthesis, suggesting a potential negative correlation between flavonoid metabolism and taxoid accumulation. Investigation of the variations in taxoids and other active ingredients will provide us with a deeper understanding of the interspecific differential accumulation of taxoids and an opportunity to accelerate the highest-yielding species breeding and resource utilization.

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