The expression of <i>TwDXS</i> in the MEP pathway specifically affects the accumulation of triptolide

Zhang, Yifeng; Zhao, Yujun; Wang, Jiadian; Hu, Tianyuan; Tong, Yuru; Gao, Jie; Huang, Luqi; Gao, Wei

doi:10.1111/ppl.13051

Cited by 15 publications

(16 citation statements)

References 33 publications

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“…Two TwDXS and one TwDXR gene were cloned from T. wilfordii , and the researchers verified their functions through colour complementation experiments 97 . Further overexpression (OE) and RNA-interference experiments confirmed that the expression of TwDXR affects the production of triptolide in T. wilfordii 98 . The TwHDR gene encodes the final enzyme of the MEP pathway, which is very important for regulating isoprene biosynthesis.…”

Section: Biosynthesis Of Triptolidementioning

confidence: 84%

Triptolide: pharmacological spectrum, biosynthesis, chemical synthesis and derivatives

Gao¹,

Zhang²,

Liu³

et al. 2021

Theranostics

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Triptolide, an abietane-type diterpenoid isolated from Tripterygium wilfordii Hook. F., has significant pharmacological activity. Research results show that triptolide has obvious inhibitory effects on many solid tumors. Therefore, triptolide has become one of the lead compounds candidates for being the next "blockbuster" drug, and multiple triptolide derivatives have entered clinical research. An increasing number of researchers have developed triptolide synthesis methods to meet the clinical need. To provide new ideas for researchers in different disciplines and connect different disciplines with researchers aiming to solve scientific problems more efficiently, this article reviews the research progress made with analyzes of triptolide pharmacological activity, biosynthetic pathways, and chemical synthesis pathways and reported in toxicological and clinical studies of derivatives over the past 20 years, which have laid the foundation for subsequent researchers to study triptolide in many ways.

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Section: Biosynthesis Of Triptolidementioning

confidence: 84%

Triptolide: pharmacological spectrum, biosynthesis, chemical synthesis and derivatives

Gao¹,

Zhang²,

Liu³

et al. 2021

Theranostics

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“…ApDXS encoded a protein of 691aa long which is in the range of plant DXSs. In general, the plant DXS protein ranged from 691 to 738aa long [19,20,[39][40][41]. The deduced amino acid sequence upon BLAST showed high similarities with plant DXS super family genes, indicating its close proximity to other functional DXS proteins.…”

Section: Discussionmentioning

confidence: 99%

“…The enhanced production of these compounds, particularly diterpene lactones can be achieved through genetic manipulation of biosynthetic pathway [15,16]. The DXS gene has made known to be a significant target for the manipulation of terpenoids biosynthesis [17][18][19][20][21]. It is essential to detect the amino acid residues prerequisite to preserve the structure and function of DXS.…”

Section: Introductionmentioning

confidence: 99%

Molecular Cloning and Differential Gene Expression Analysis of 1-Deoxy-D-xylulose 5-Phosphate Synthase (DXS) in Andrographis paniculata (Burm. f) Nees

et al. 2020

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Andrographis paniculata 1-deoxy-D-xylulose-5-phosphate synthase (ApDXS) gene (GenBank Accession No MG271749.1) was isolated and cloned from leaves for the first time. Expression of ApDXS gene was carried out in Escherichia coli Rosetta cells. Tissue-specific ApDXS gene expression by quantitative RT-PCR (qRT-PCR) revealed maximum fold expression in the leaves followed by stem and roots. Further, the differential gene expression profile of Jasmonic acid (JA)-elicited in vitro adventitious root cultures showed enhanced ApDXS expression compared to untreated control cultures. A. paniculata 3-hydroxy-3-methylglutaryl-coenzyme A reductase (ApHMGR) gene expression was also studied where it was up-regulated by JA elicitation but showed lower expression compared to ApDXS. The highest expression of both genes was found at 25 µm JA elicitation followed by 50 µm. HPLC data indicated that the transcription levels were correlated with increased andrographolide accumulation. The peak level of andrographolide accumulation was recorded at 25 μM JA (9.38-fold) followed by 50 µM JA (7.58-fold) in elicitation treatments. The in silico generated ApDXS 3D model revealed 98% expected amino acid residues in the favored and 2% in the allowed regions of the Ramachandran plot with 92% structural reliability. Further, prediction of conserved domains and essential amino acids [Arg (249, 252, 255), Asn (307) and Ser (247)] involved in ligand/ inhibitor binding was carried out by in silico docking studies. Our present findings will generate genomic information and provide a blueprint for future studies of ApDXS and its role in diterpenoid biosynthesis in A. paniculata.

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“…The first two rate‐limiting enzymes in this pathway are 1‐deoxy‐ d ‐xylulose‐5‐phosphate synthase (DXS) and 1‐deoxy‐d‐xylulose‐5‐phosphate reductoisomerase (DXR). GA‐3‐P and pyruvate could be converted into MEP through catalysis by DXS and DXR, sequentially 45,46 . In 2015, genes encoding Tw DXS and Tw DXR were cloned from T. wilfordii , and they were all highly expressed in the roots 47 .…”

Section: Biosynthesismentioning

confidence: 99%

Biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of the quinone‐methide triterpenoid celastrol

Lü

Liu

Zhou

et al. 2020

Medicinal Research Reviews

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Celastrol, a quinone‐methide triterpenoid, was extracted from Tripterygium wilfordii Hook. F. in 1936 for the first time. Almost 70 years later, it is considered one of the molecules most likely to be developed into modern drugs, as it exhibits notable bioactivity, including anticancer and anti‐inflammatory activity, and exerts antiobesity effects. In addition, the molecular mechanisms underlying its bioactivity are being widely studied, which offers new avenues for its development as a pharmaceutical reagent. Owing to its potential therapeutic effects and unique chemical structure, celastrol has attracted considerable interest in the fields of organic, biosynthesis, and medicinal chemistry. As several steps in the biosynthesis of celastrol have been revealed, the mechanisms of key enzymes catalyzing the formation and postmodifications of the celastrol scaffold have been gradually elucidated, which lays a good foundation for the future heterogeneous biosynthesis of celastrol. Chemical synthesis is also an effective approach to obtain celastrol. The total synthesis of celastrol was realized for the first time in 2015, which established a new strategy to obtain celastroid natural products. However, owing to the toxic effects and suboptimal pharmacological properties of celastrol, its clinical applications remain limited. To search for drug‐like derivatives, several structurally modified compounds were synthesized and tested. This review focuses primarily on the latest research progress in the biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of celastrol. We anticipate that this paper will facilitate a more comprehensive understanding of this promising compound and provide constructive references for future research in this field.

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The expression of TwDXS in the MEP pathway specifically affects the accumulation of triptolide

Cited by 15 publications

References 33 publications

Triptolide: pharmacological spectrum, biosynthesis, chemical synthesis and derivatives

Triptolide: pharmacological spectrum, biosynthesis, chemical synthesis and derivatives

Molecular Cloning and Differential Gene Expression Analysis of 1-Deoxy-D-xylulose 5-Phosphate Synthase (DXS) in Andrographis paniculata (Burm. f) Nees

Biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of the quinone‐methide triterpenoid celastrol

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