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result(s) for
"Taxus - chemistry"
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An Integrated Strategy Based on 10-DAB Extraction and In Situ Whole-Cell Biotransformation of Renewable Taxus Needles to Produce Baccatin III
by
Kou, Ping
,
Wang, He
,
Zhang, Yuchi
in
10-deacetylbaccatin III-10-β-O-acetyltransferase
,
acetyl-CoA supply
,
Acetyltransferases - genetics
2024
Baccatin III is a crucial precursor in the biosynthesis pathway of paclitaxel. Its main sources are extraction from Taxus or chemical synthesis using 10-deacetylbaccatin III (10-DAB) as substrate. However, these preparation approaches exhibit serious limitations, including the low content of baccatin III in Taxus and the complicated steps of chemical synthesis. Heterologous expression of 10-deacetylbaccatin III-10-O-acetyltransferase (TcDBAT) in microbial strains for biotransformation of 10-DAB is a promising alternative strategy for baccatin III production. Here, the promotion effects of glycerol supply and slightly acidic conditions with a low-temperature on the catalysis of recombinant TcDBAT strain were clarified using 10-DAB as substrate. Taxus needles is renewable and the content of 10-DAB is relatively high, it can be used as an effective source of the catalytic substrate 10-DAB. Baccatin III was synthesized by integrating the extraction of 10-DAB from renewable Taxus needles and in situ whole-cell catalysis in this study. 40 g/L needles were converted into 20.66 mg/L baccatin III by optimizing and establishing a whole-cell catalytic bioprocess. The method used in this study can shorten the production process of Taxus extraction for baccatin III synthesis and provide a reliable strategy for the efficient production of baccatin III by recombinant strains and the improvement of resource utilization rate of Taxus needles.
Journal Article
Optimization of Taxol Extraction Process Using Response Surface Methodology and Investigation of Temporal and Spatial Distribution of Taxol in Taxus mairei
by
Chen, Yiming
,
Wang, Tao
,
Xie, Yinfeng
in
Chemical Fractionation - methods
,
Experiments
,
Leaves
2021
Taxus mairei is an important source for industrial extraction of taxol in China. However, the standard and steps of extraction are currently not uniform, which seriously affects the taxol yield. In the present study, the influence of four factors (methanol concentration, solid-liquid ratio, ultrasonic extraction temperature, and ultrasonic extraction time) on the taxol yield was successively explored in T. mairei. A response surface methodology (RSM) was used to optimize the extraction process based on the single-factor experiments above. The optimal conditions were as follows: methanol concentration was 90%, solid-liquid ratio was 1:15 (g/mL), ultrasonic extraction temperature was 40 °C and ultrasonic extraction time was 60 min. Moreover, the twigs and needles from T. mairei with different tree ages were treated by the optimum extraction process, which further revealed temporal and spatial distribution of taxol in the reproducible tissues. Interestingly, the taxol content was relatively higher in needles of T. ‘Jinxishan’ (a cultivar from T. mairei with yellow aril, FY), but was less in FY twigs. The accumulation of taxol in twigs and leaves of females (with red aril, FR) was significantly higher than that of males (M); however, the content showed a decreasing trend with the increasing tree ages. Therefore, it is suitable to increase the proportion of female trees especially the FY leaves as raw materials for the industrial production of taxol from T. mairei, and the tree ages should be better controlled at 3–7 years.
Journal Article
Improving 10-deacetylbaccatin III-10-β-O-acetyltransferase catalytic fitness for Taxol production
2017
The natural concentration of the anticancer drug Taxol is about 0.02% in yew trees, whereas that of its analogue 7-β-xylosyl-10-deacetyltaxol is up to 0.5%. While this compound is not an intermediate in Taxol biosynthetic route, it can be converted into Taxol by de-glycosylation and acetylation. Here, we improve the catalytic efficiency of 10-deacetylbaccatin III-10-
O
-acetyltransferase (DBAT) of
Taxus
towards 10-deacetyltaxol, a de-glycosylated derivative of 7-β-xylosyl-10-deacetyltaxol to generate Taxol using mutagenesis. We generate a three-dimensional structure of DBAT and identify its active site using alanine scanning and design a double DBAT mutant (DBAT
G38R/F301V
) with a catalytic efficiency approximately six times higher than that of the wild-type. We combine this mutant with a β-xylosidase to obtain an
in vitro
one-pot conversion of 7-β-xylosyl-10-deacetyltaxol to Taxol yielding 0.64 mg ml
−1
Taxol in 50 ml at 15 h. This approach represents a promising environmentally friendly alternative for Taxol production from an abundant analogue.
Taxol is a widely used anticancer drug that is found in very low amounts in the bark of Taxus plants. Here, the authors improve the catalytic fitness of DBAT, an enzyme that catalyses the conversion of tree by products into taxol, enabling the design of an
in vitro
biochemical systems for taxol production.
Journal Article
Metabolic Variations of Flavonoids in Leaves of T. media and T. mairei Obtained by UPLC-ESI-MS/MS
by
Zhuang, Weibing
,
Wang, Tao
,
Wang, Zhong
in
Anthocyanins - biosynthesis
,
Anthocyanins - metabolism
,
Biosynthesis
2019
The needles of Taxus species contain a large number of bioactive compounds, such as flavonoids. In the present study, the total flavonoid content in leaves of Taxus media and Taxus mairei was 19.953 and 14.464 mg/g, respectively. A total of 197 flavonoid metabolites (70 flavones, 42 flavonols, 26 flavone C-glycosides, 20 flavanones, 15 anthocyanins, 13 isoflavones, 6 flavonolignans, and 5 proanthocyanidins) were identified for the first time by a widely targeted Ultra Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (UPLC-ESI-MS/MS) method within the two Taxus species, containing 160 common metabolites, with 37 unique metabolites merely determined in T. mairei or T. media. Moreover, 42 differential flavonoid metabolites were screened in the two Taxus species, which showed specific metabolic patterns in isoflavonoid biosynthesis, anthocyanin biosynthesis, and flavone and flavonol biosynthesis pathways. Compared to T. mairei, a more activated phenylpropanoid pathway was found in T. media, which could be responsible for the higher content of total flavonoids in T. media. Our results provide new insights into the diversity of flavonoid metabolites between T. mairei and T. media, and provide a theoretical basis for the sufficient utilization of Taxus species and the development of novel drugs.
Journal Article
Seasonal Dynamics of Metabolites in Needles of Taxus wallichiana var. mairei
by
Pan, Cun-De
,
Zheng, Zan-Sheng
,
Yang, Li
in
Cancer
,
Chromatography, High Pressure Liquid - methods
,
Flavones - analysis
2016
Seasonal variations of the phytochemicals contents in needles of T. wallichiana var. mairei due to the effects of growth meteorological parameters were investigated in this study. The needles of T. wallichiana var. mairei were collected from different months and the contents of taxoids (paclitaxel, 10-deacetylbaccatin III (10-DAB), baccatin III, cephalomannine, 10-deacetyltaxol (10-DAT)), flavones (ginkgetin, amentoflavone, quercetin) and polysaccharides were quantified by ultra performance liquid chromatography (UPLC) and the resonance light scattering (RIL) method. The content of taxoids gave the highest level of 1.77 ± 0.38 mg·g−1 in January, and the lowest value of 0.61 ± 0.08 mg·g−1 in September. Unlike taxoids, the content of flavonoids was the highest in August. The content of polysaccharides reached peak value of 28.52 ± 0.57 mg·g−1 in September, which was two times higher than the lowest content of 9.39 ± 0.17 mg·g−1 in January. The contents of paclitaxel, 10-DAB, 10-DAT and polysaccharides significantly depended on meteorological parameters. The mean of minimum temperature (R = −0.61) and length of daylight (R = −0.60) were significantly correlated to 10-DAB content, while 10-DAT level showed significant correlation with length of daylight (R = −0.70) and relative humidity (R = 0.70). In addition, temperature had significantly negative effect on the content of paclitaxel and a significantly positive effect on that of polysaccharides. This study enriched the knowledge on the accumulation pattern of metabolites and could help us to determine the collecting time of T. wallichiana var. mairei for medicinal use.
Journal Article
Profiling of Taxoid Compounds in Plant Cell Cultures of Different Species of Yew (Taxus spp.)
by
Demidova, Elena V.
,
Kochkin, Dmitry V.
,
Nosov, Alexander M.
in
14-hydroxylated taxoids
,
Analytical chemistry
,
Biomass
2023
Plant cell cultures of various yew species are a profitable source of taxoids (taxane diterpenoids) with antitumor activity. So far, despite intensive studies, the principles of the formation of different groups of taxoids in cultured in vitro plant cells have not been fully revealed. In this study, the qualitative composition of taxoids of different structural groups was assessed in callus and suspension cell cultures of three yew species (Taxus baccata, T. canadensis, and T. wallichiana) and two T. × media hybrids. For the first time, 14-hydroxylated taxoids were isolated from the biomass of the suspension culture of T. baccata cells, and their structures were identified by high-resolution mass spectrometry and NMR spectroscopy as 7β-hydroxy-taxuyunnanin C, sinenxane C, taxuyunnanine C, 2α,5α,9α,10β,14β-pentaacetoxy-4(20), 11-taxadiene, and yunnanxane. UPLC–ESI-MS screening of taxoids was performed in more than 20 callus and suspension cell lines originating from different explants and grown in over 20 formulations of nutrient media. Regardless of the species, cell line origin, and conditions, most of the investigated cell cultures retained the ability to form taxane diterpenoids. Nonpolar 14-hydroxylated taxoids (in the form of polyesters) were predominant under in vitro culture conditions in all cell lines. These results, together with the literature data, suggest that dedifferentiated cell cultures of various yew species retain the ability to synthesize taxoids, but predominantly of the 14-OH taxoid group compared to the 13-OH taxoids found in plants.
Journal Article
Research Progress on Taxus Extraction and Formulation Preparation Technologies
2024
Taxus, as a globally prevalent evergreen tree, contains a wealth of bioactive components that play a crucial role in the pharmaceutical field. Taxus extracts, defined as a collection of one or more bioactive compounds extracted from the genus Taxus spp., have become a significant focus of modern cancer treatment research. This review article aims to delve into the scientific background of Taxus extracts and their considerable value in pharmaceutical research. It meticulously sifts through and compares various advanced extraction techniques such as supercritical extraction, ultrasound extraction, microwave-assisted extraction, solid-phase extraction, high-pressure pulsed electric field extraction, and enzymatic extraction, assessing each technology’s advantages and limitations across dimensions such as extraction efficiency, extraction purity, economic cost, operational time, and environmental impact, with comprehensive analysis results presented in table form. In the area of drug formulation design, this paper systematically discusses the development strategies for solid, liquid, and semi-solid dosage forms based on the unique physicochemical properties of Taxus extracts, their intended medical uses, and specific release characteristics, delving deeply into the selection of excipients and the critical technical issues in the drug preparation process. Moreover, the article looks forward to the potential directions of Taxus extracts in future research and medical applications, emphasizing the urgency and importance of continuously optimizing extraction methods and formulation design to enhance treatment efficacy, reduce production costs, and decrease environmental burdens. It provides a comprehensive set of preparation techniques and formulation optimization schemes for researchers in cancer treatment and other medical fields, promoting the application and development of Taxus extracts in pharmaceutical sciences.
Journal Article
Red Arils of Taxus baccata L.—A New Source of Valuable Fatty Acids and Nutrients
by
Skoczylas, Łukasz
,
Słupski, Jacek
,
Rutkowska, Jaroslawa
in
amino acids
,
Amino Acids - chemistry
,
Animals
2021
The aim of this study, focused on the nutritional value of wild berries, was to determine the contents of macronutrients, profiles of fatty (FAs) and amino acids (AAs), and the contents of selected elements in red arils (RA) of Taxus baccata L., grown in diverse locations in Poland. Protein (1.79–3.80 g/100 g) and carbohydrate (18.43–19.30 g/100 g) contents of RAs were higher than in many cultivated berries. RAs proved to be a source of lipids (1.39–3.55 g/100 g). Ten out of 18 AAs detected in RAs, mostly branched-chain AAs, were essential AAs (EAAs). The EAAs/total AAs ratio approximating were found in animal foods. Lipids of RA contained seven PUFAs, including those from n-3 family (19.20–28.20 g/100 g FA). Polymethylene-interrupted FAs (PMI-FAs), pinolenic 18:3Δ5,9,12; sciadonic 20:3Δ5,11,14, and juniperonic 20:4Δ5,11,14,17, known as unique for seeds of gymnosperms, were found in RAs. RAs may represent a novel dietary source of valuable n-3 PUFAs and the unique PMI-FAs. The established composition of RAs suggests it to become a new source of functional foods, dietary supplements, and valuable ingredients. Because of the tendency to accumulate toxic metals, RAs may be regarded as a valuable indicator of environmental contamination. Thus, the levels of toxic trace elements (Al, Ni, Cd) have to be determined before collecting fruits from natural habitats.
Journal Article
Research on the Medicinal Chemistry and Pharmacology of Taxus × media
by
Zhang, Ni
,
Gao, Xinyu
,
Xie, Weidong
in
Animals
,
Antioxidants - chemistry
,
Antioxidants - pharmacology
2024
Taxus × media, belonging to the genus Taxus of the Taxaceae family, is a unique hybrid plant derived from a natural crossbreeding between Taxus cuspidata and Taxus baccata. This distinctive hybrid variety inherits the superior traits of its parental species, exhibiting significant biological and medicinal values. This paper comprehensively analyzes Taxus × media from multiple dimensions, including its cultivation overview, chemical composition, and multifaceted applications in the medical field. In terms of chemical constituents, this study delves into the bioactive components abundant in Taxus × media and their pharmacological activities, highlighting the importance and value of these components, including paclitaxel, as the lead compounds in traditional medicine and modern drug development. Regarding its medicinal value, the article primarily discusses the potential applications of Taxus × media in combating tumors, antibacterial, anti-inflammatory, and antioxidant activities, and treating diabetes. By synthesizing clinical research and experimental data, the paper elucidates the potential and mechanisms of its primary active components in preventing and treating these diseases. In conclusion, Taxus × media demonstrates its unique value in biological research and tremendous potential in drug development.
Journal Article
Advancements in the Cultivation, Active Components, and Pharmacological Activities of Taxus mairei
2024
Taxus mairei (Lemée and H.Lév.) S.Y.Hu, indigenous to the southern regions of China, is an evergreen tree belonging to the genus Taxus of the Taxaceae family. Owing to its content of various bioactive compounds, it exhibits multiple pharmacological activities and has been widely applied in clinical medicine. This article comprehensively discusses the current state of cultivation, chemical constituents, applications in the pharmaceutical field, and the challenges faced by T. mairei. The paper begins by detailing the ecological distribution of T. mairei, aiming to provide an in-depth understanding of its origin and cultivation overview. In terms of chemical composition, the article thoroughly summarizes the extracts and monomeric components of T. mairei, unveiling their pharmacological activities and elucidating the mechanisms of action based on the latest scientific research, as well as their potential as lead compounds in new drug development. The article also addresses the challenges in the T. mairei research, such as the difficulties in extracting and synthesizing active components and the need for sustainable utilization strategies. In summary, T. mairei is a rare species important for biodiversity conservation and demonstrates significant research and application potential in drug development and disease treatment.
Journal Article