Taxanes

紫杉烷
  • 文章类型: Journal Article
    目的:紫杉烷类是广泛使用的化疗药物,经常引起指甲变化,对患者的生活质量有显著影响。尽管紫杉烷引起的指甲毒性很普遍,关于预防或治疗紫杉烷引起的指甲改变的循证管理策略的可用数据有限.因此,我们的目标是深入了解预防,治疗,并通过对医生进行问卷调查来评估日本癌症患者的指甲变化,药剂师,和护士参与肿瘤治疗。
    方法:问题涉及预防方法,评估实践,以及各种指甲疾病的治疗方法。问卷于2022年3月1日分发,回复截止日期为2022年12月1日。
    结果:在分发的120份问卷中,88人(73.3%)被退回,所有这些都经过了分析。受访者包括69名医生(32名肿瘤学家,26位乳房外科医生,6名皮肤科医生,3名产科医生/妇科医生,1名胃肠病外科医生,和1名泌尿科医生),9名药剂师,10名护士。预防措施包括保湿(58.0%),保护(42.0%),冷却疗法(37.5%),清洁度(33.0%)。大约70%的受访者使用不良事件通用标准(CTCAE)。而大约30%的人没有使用特定的评估方法。关于抗微生物剂或皮质类固醇软膏治疗的意见各不相同;然而,所有严重病例均由皮肤科医生转诊.
    结论:我们的调查显示,在日本的临床实践中,化疗引起的指甲变化的管理各不相同。这些发现强调了标准化管理策略和进一步研究的必要性。
    OBJECTIVE: Taxanes are widely used chemotherapeutic agents that frequently cause nail changes and have a significant impact on patients\' quality of life. Despite the prevalence of taxane-induced nail toxicity, limited data are available regarding evidence-based management strategies for the prevention or treatment of taxane-induced nail changes. Therefore, we aimed to gain insights into the prevention, treatment, and evaluation of nail changes in patients with cancer in Japan by conducting a questionnaire survey of physicians, pharmacists, and nurses involved in oncology treatment.
    METHODS: The questions addressed prophylactic methods, evaluation practices, and treatment approaches for various nail disorders. The questionnaires were distributed on March 1, 2022, with a response deadline of December 1, 2022.
    RESULTS: Of the 120 questionnaires distributed, 88 (73.3%) were returned, and all of them were analyzed. The respondents included 69 physicians (32 oncologists, 26 breast surgeons, 6 dermatologists, 3 obstetricians/gynecologists, 1 gastroenterological surgeon, and 1 urologist), 9 pharmacists, and 10 nurses. Prophylactic measures included moisturizing (58.0%), protection (42.0%), cooling therapy (37.5%), and cleanliness (33.0%). Approximately 70% of the respondents used the Common Criteria for Adverse Events (CTCAE), while approximately 30% did not use a specific evaluation method. Opinions regarding treatment with antimicrobial or corticosteroid ointments varied; however, all severe cases were referred by dermatologists.
    CONCLUSIONS: Our survey revealed that the management of chemotherapy-induced nail changes varies in clinical practice in Japan. These findings emphasize the need for standardized management strategies and further research.
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  • 文章类型: Journal Article
    本研究旨在研究七个土耳其榛子(CorylusavellanaL.)基因型的可食用和非可食用部分的抗癌紫杉烷概况。榛子是富含营养和抗氧化剂的健康食品之一。它的定期食用与降低患冠心病和癌症的风险有关。榛子已被描述为产生紫杉烷的植物来源,紫杉烷被广泛用于许多癌症。Türkiye是榛子文化的故乡,拥有自己的品种。研究土耳其榛子基因型不同部位的抗癌紫杉烷概况对于从制药和食品工业的角度显示该植物的潜力和价值很重要。
    在这项研究中,绿叶盖(GLC)和硬壳(HS)(非可食用部分),无皮肤内核(SKs),棕色皮肤(BS),和Kelak²ldak的棕色皮肤内核(BSKs)(可食用部分),Sivri,Tombul,帕拉兹,和卡尔纳卡拉作为标准,使用Ham和SivriYalº作为本地基因型。将每种基因型的五个部分研磨成粉末并消除至小于80目的尺寸。每个部分使用己烷和甲醇提取10-脱乙酰浆果蛋白酶III(10-DABIII),baccatinIII(BACIII),头孢菌素,和紫杉醇分析,三个重复。样品和标准品用乙腈:水梯度法在NOVASpher100苯基-己基C18色谱柱上,用228nm紫外检测器和1.0mL/min流速的高效液相色谱反相系统进行分析。MicrosoftOfficeExcel,2016年,采用Jamovi2.3版的方差分析进行统计和数据分析,连续。
    榛子零件在最高10-DABIII(HamHS,9,15μg/g),BACIII(卡勒恩卡拉BS,7.24μg/g),头孢霉素(SivriYaoll²BSs,6.37μg/g),和紫杉醇(HamBSKs,4.36μg/g)。而HS,BSKs,在所有分析的基因型中,BS富含紫杉烷,SKs,和GLC对于抗癌紫杉烷仍然有限。
    这是第一份报告,揭示了土耳其榛子紫杉烷含量的差异,包括以前未经测试的标准和当地基因型及其部分。基因型和榛子部分之间的显着差异预计将突出食用带有BS的生土耳其榛子的健康益处及其可能用作功能性食品。这些结果为阐明土耳其榛子及其副产品的生物活性潜力提供了更多信息,并为食品和制药行业提供了具有抗癌前景的有希望的资源。
    UNASSIGNED: This study aimed to investigate the anticancer taxane profiles of edible and non-edible parts of seven Turkish hazelnut (Corylus avellana L.) genotypes. Hazelnut is one of the healthy foods rich in nutrients and antioxidants. Its regular consumption is associated with a reduced risk of coronary heart disease and cancer. Hazelnut has been described as a plant source that produces taxanes which are widely used in many cancers. Türkiye is a homeland of hazelnut culture and has its own cultivars. Investigation of anticancer taxane profiles in different parts of Turkish hazelnut genotypes is important to show the potential and value of this plant from the perspective of the pharmaceutical and food industries.
    UNASSIGNED: In this study, green leafy covers (GLCs) and hard shells (HSs) (non-edible parts), skinless kernels (SKs), brown-skins (BSs), and brown-skinned kernels (BSKs) (edible parts) of Çakıldak, Sivri, Tombul, Palaz, and Kalınkara as standard and Ham and Sivri Yağlı as local genotypes were used. The five parts of each genotype were ground to powder and eliminated to a size of less than 80 mesh. Each part was extracted using hexane and methanol for 10-deacetylbaccatin III (10-DAB III), baccatin III (BAC III), cephalomannine, and paclitaxel analyses in three replicates. Samples and standards were analyzed by acetonitrile: water gradient method on NOVA Spher 100 Phenyl-Hexyl C18 column inhigh-performance liquid chromatography reverse phase system with 228 nm ultraviolet detector and 1.0 mL/min flow rate. Microsoft Office Excel, 2016, and analysis of variance Jamovi Version 2.3 were used for statistical and data analysis, consecutively.
    UNASSIGNED: Hazelnut parts differed to a very high degree from each other in terms of the highest amount of 10- DAB III (Ham HSs, 9,15 μg/g), BAC III (Kalınkara BSs, 7.24 μg/g), cephalomannine (Sivri Yağlı BSs, 6.37 μg/g), and paclitaxel (Ham BSKs, 4.36 μg/g) they contained. While HSs, BSKs, and BSs were rich in taxanes in all of the analyzed genotypes, SKs, and GLCs remain limited for anticancer taxanes.
    UNASSIGNED: This is the first report that revealed the differences in taxane contents of Turkish hazelnuts including previously untested standard and local genotypes and their parts. Significant differences between genotype and hazelnut parts are expected to highlight the health benefits of consuming raw Turkish hazelnut with BSs and their possible use as a functional food. These results add more information to elucidate the bioactive potential of Turkish hazelnuts and their by-products and provide a promising resource for the food and pharmaceutical industry with an anticancer perspective.
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  • 文章类型: Journal Article
    紫杉属物种含有抗癌生物碱紫杉醇,以及其他结构相似且可能与紫杉醇有效的紫杉烷。据报道,一些紫杉树种中紫杉烷的组织特异性分布模式和季节性变化;然而,Taxuscuspidata中的紫杉烷仍然存在不足。
    通过低温飞行时间二次离子质谱和扫描电子显微镜(cryo-TOF-SIMS/SEM)可视化和液相色谱-质谱(LC-MS)定量分析,研究了夏末和春季季节的冷冻固定T.cuspidata横向表面中八种紫杉烷的径向分布。通过光学显微镜观察,在特定组织中进一步表征了目标紫杉烷类的数量和分布模式的季节性差异。
    紫杉烷的总量在夏末比春季高。此外,紫杉烷的径向分布通常在韧皮部中发现较高的浓度,形成层和周围层的下层,最新形成的木质部,不同的紫杉烷显示出几种不同季节的模式,这被认为与季节性植物的生理行为有关。此外,在细胞水平上研究了bacchatinIII(BAC)的分布,在特定细胞中被认为表明其在虎杖茎中的径向和轴向运输。表征紫杉烷在虎杖茎中的微观分布有望在进一步研究其生物合成和植物行为中发挥作用。
    UNASSIGNED: Taxus species contain the anticancer alkaloid paclitaxel, as well as other taxanes similar in structure and potentially in effect to paclitaxel. Tissue-specific distribution patterns and seasonal variations of taxanes in some Taxus species have been reported; however, it is still under-presented for the taxanes in Taxus cuspidata.
    UNASSIGNED: The radial distributions of eight taxanes in the transverse surface of freeze-fixed T. cuspidata stems from the late summer and the spring seasons were investigated by cryo-time-of-flight secondary ion mass spectrometry and scanning electron microscopy (cryo-TOF-SIMS/SEM) visualization and liquid chromatography-mass spectrometry (LC-MS) quantitative analysis. By optical microscopic observation, seasonal differences in the amounts and distribution patterns of target taxanes were further characterized in specific tissues.
    UNASSIGNED: The overall amount of taxanes was higher in the late summer than in the spring. Also, taxanes\' radial distribution was generally found at higher concentration in the phloem, the cambium and lower level in the periderm, the latest-forming xylem, with different taxanes showing several patterns with distinction between seasons, which were considered related to seasonal plant physiological behaviors. In addition, the distribution of baccatin III (BAC) was investigated at the cellular level, which was regarded in specific cells suggesting its transport in the radial and axial directions in the T. cuspidata stem. Characterizing the microscopic distribution of taxanes in the T. cuspidata stem is expected to play a role in the further study of their biosynthesis and in planta behaviors.
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  • 文章类型: Journal Article
    背景:SLC2A1增强紫杉烷类对非小细胞肺癌(NSCLC)的化学抗性的机制仍然是一个谜。
    方法:对不同数据集的SLC2A1表达模式和预后进行调查,以及我们内部收集的样本,进行了。此外,通过体外实验进一步研究了SLC2A1的生物学功能。该研究还使用CCK-8,膜联蛋白-V检查了NSCLC对紫杉烷的化学抗性,和caspase-3测定。此外,紫杉烷类对SLC2A1表达的影响通过蛋白质印迹分析确定.通过流式细胞术和代谢组学技术检查SLC2A1对CSC形成的影响。最后,使用单细胞测序和细胞聊天分析了SLC2A1对肿瘤微环境的影响.
    结果:在本调查中,观察到SLC2A1在NSCLC肿瘤组织中的表达升高,表现出与预后较差的显着关联。SLC2A1过表达促进NSCLC细胞增殖,入侵,迁移,化学抗性,CD90+和EpCAM+CSCs的形成。基于SLC2A1和EpCAM表达对NSCLC细胞进行分类。SLC2A1highEpCAM+CSC对紫杉烷类具有更高的化学抗性。SLC2A1和EpCAM高表达的NSCLC患者预后较差。机械上,SLC2A1通过激活糖酵解促进CD90+和EpCAM+CSC的形成。最后,SLC2A1低肿瘤细胞通过HLA-A促进CD8+T细胞功能,B,C,通过HLA-E抑制NK细胞功能
    结论:一起,SLC2A1在增强紫杉烷类对NSCLC的化学抗性中起重要作用。
    BACKGROUND: The mechanisms by which SLC2A1 enhances chemo-resistance of taxanes to non-small cell lung cancer (NSCLC) remains enigmatic.
    METHODS: An investigation into the SLC2A1 expression pattern and prognosis across diverse datasets, as well as our internally collected samples, was undertaken. Additionally, the biological function of SLC2A1 was further delved into through in vitro experiments. The study also examined the chemo-resistance of NSCLC to taxanes using CCK-8, Annexin-V, and caspase-3 assays. Furthermore, the impact of taxanes on SLC2A1 expression was determined via western blot analysis. The effects of SLC2A1 on the formation of CSCs was examined via flow cytometry and metabolomics techniques. Finally, the impact of SLC2A1 on the tumor microenvironment was analyzed using single-cell sequencing and cellchat.
    RESULTS: In the present investigation, it was observed that there was an elevated expression of SLC2A1 in NSCLC tumor tissues, which exhibited a significant association with a poorer prognosis. SLC2A1 overexpression in vitro promoted NSCLC cell proliferation, invasion, migration, chemo-resistance, and the formation of CD90+ and EpCAM+ CSCs. NSCLC cells were categorized based on SLC2A1 and EpCAM expression. SLC2A1highEpCAM+ CSCs were more chemo-resistance to taxanes. NSCLC patients with high SLC2A1 and EpCAM expression had poorer prognosis. Mechanically, SLC2A1 promoted the formation of CD90+ and EpCAM+ CSCs via activating glycolysis. Finally, SLC2A1low tumor cells promoted CD8+T cell function via HLA-A, B, C, and suppressed NK cell function via HLA-E.
    CONCLUSIONS: Together, SLC2A1 plays an important role in enhancing chemo-resistance of taxanes to NSCLC.
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  • 文章类型: Journal Article
    这里,我们揭示了卡巴他赛(CBZ)诱导的PC-3去势耐药转移性前列腺癌细胞(mCRPC)凋亡的可逆性。通过膜联蛋白V评估在不同恢复期去除CBZ后PC-3细胞从凋亡中的恢复,DNA损伤,氧化损伤,线粒体膜去极化,和半胱天冬酶激活。我们的结果表明,CBZ的给药导致PC-3细胞凋亡72h。然而,恢复的细胞表现出减少的核损伤,质膜破裂,ROS水平,在PC-3细胞中去除特别是1nMCBZ持续24小时恢复期后,释放细胞色素c水平和caspase-3激活,上调Bcl-2表达。我们的研究表明,CBZ处理的PC-3细胞可以在凋亡细胞死亡后恢复。然而,高级分子分析应阐明PC-3mCRPC细胞中恢复的分子机制与紫杉烷反应或抗性之间的关系。
    Here, we revealed the reversibility of cabazitaxel (CBZ)-induced apoptosis in PC-3 castration resistant metastatic prostate cancer cells (mCRPC) through the hallmarks of apoptosis. The recovery of PC-3 cells from apoptosis upon removal of CBZ at different recovery periods was evaluated by Annexin V, DNA damage, oxidative damage, mitochondrial membrane depolarization, and caspase activation. Our results showed that the administration of CBZ caused apoptosis for 72 h in PC-3 cells. However, recovered cells exhibited decreased nuclear damage, plasma membrane disruption, ROS level, release cytochrome c level and caspase-3 activation with upregulation of Bcl-2 expression upon removal of especially 1 nM CBZ for 24 h recovery period in PC-3 cells. Our study indicates that CBZ treated PC-3 cells can recover after apoptotic cell death. However, advanced molecular analysis should elucidate the relationship between the molecular mechanisms of recovery and taxane response or resistance in PC-3 mCRPC cells.
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  • 文章类型: Case Reports
    紫杉烷相关性黄斑囊样水肿(CME)是紫杉烷类药物的罕见并发症,化疗药物.我们报告了一名47岁的汉族男子,他将我们的眼科中心转诊为视力下降,双眼视觉畸变持续两周。两周前,他接受了六个月化疗的最后一个周期,包括用于下咽恶性肿瘤的紫杉醇。最佳矫正视力(BCVA)为0.4OD和0.1OS。黄斑光学相干断层扫描显示显著的双侧CME,荧光素血管造影术(FA)显示荧光素在晚期聚集而无泄漏。玻璃体内注射700μg地塞米松(DEX)植入物施用于左眼,13天后施用于右眼。两个月后,黄斑形态恢复正常。第一次访问一年后,在OCT上,BCVA为1.0OD和0.8OS,标准黄斑。总之,玻璃体内DEX植入可能是紫杉烷相关CME的有效辅助治疗.
    Taxane-related cystoid macular edema (CME) is a rare complication of the taxoid medication, a chemotherapeutic drug. We report a 47-year-old Han Chinese man referred to our Eye Center for decreased vision with visual distortion in both eyes for two weeks. Two weeks prior, he received the last cycle of his six-monthly chemotherapy, including paclitaxel for hypopharyngeal malignancy. The best-corrected visual acuity (BCVA) was 0.4 OD and 0.1 OS. Macular optical coherence tomography showed significant bilateral CME, and fluorescein angiography (FA) revealed the fluorescein pooling at the late phase without leakage. Intravitreal 700 μg dexamethasone (DEX) implant was applied to the left eye and 13 days after to the right eye. Two months later, the macular morphology recovered to normal. One year after the first visit, the BCVA was 1.0 OD and 0.8 OS with standard macula on OCT. In conclusion, the intravitreal DEX implant might be an effective adjuvant treatment for taxane-related CME.
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  • 文章类型: Journal Article
    目的:该研究调查了冷冻疗法在减轻化疗引起的周围神经病变(CIPN)中的疗效,化疗的不良反应,通常导致剂量减少或治疗中断。
    方法:本研究注册于PROSPERO(CRD42023428936)。使用PubMed进行了文献检索,Embase,和Cochrane图书馆数据库。纳入研究冷冻疗法对CIPN影响的随机和非随机对照试验进行系统评价和荟萃分析。预防的主要结果是CIPN的发生率。
    结果:我们确定了17项试验,涉及2,851例患者。总的来说,11项试验比较了冷冻治疗组和对照组的CIPN发生率。观察到化疗中点和结束时CIPN的发生率存在显着差异,风险比(RR)为0.23(95%置信区间[CI]=0.13至0.43)和0.54(95%CI=0.33至0.88),分别。冷冻疗法也显著降低了感觉CIPN的发生率,RR为0.67(95%CI=0.49至0.92)。此外,冷冻治疗显示妇科癌症患者CIPN的发生率显著降低(RR=0.24,95%CI=0.14~0.41).化疗后的整体生活质量评分明显良好(标准化平均差=1.43;95%CI=0.50至2.36),冷冻治疗可缓解神经性症状。
    结论:冷冻疗法对CIPN的发展具有明显的预防作用,为接受化疗的患者提供实质性的症状缓解和生活质量改善。通过使用冷冻手套和袜子进行冷冻治疗,或连续流冷却系统,最佳在化疗前15分钟开始,并在化疗后15分钟结束,被推荐用于实现最大的治疗效果。
    OBJECTIVE: The study investigates cryotherapy\'s efficacy in mitigating Chemotherapy-induced peripheral neuropathy (CIPN), an adverse effect of chemotherapy that often leads to dosage reduction or treatment discontinuation.
    METHODS: The study was registered with PROSPERO (CRD42023428936). A literature search was conducted using the PubMed, Embase, and Cochrane Library databases. Randomized and nonrandomized controlled trials that investigated the effects of cryotherapy on CIPN were included for systematic review and meta-analysis. The primary outcome for prevention was the incidence of CIPN.
    RESULTS: We identified 17 trials involving 2,851 patients. In total, 11 trials compared the incidence of CIPN between cryotherapy and control groups. Significant differences in the incidence of CIPN at the midpoint and end of chemotherapy were observed, with risk ratios (RRs) of 0.23 (95% confidence interval [CI] = 0.13 to 0.43) and 0.54 (95% CI = 0.33 to 0.88), respectively. Cryotherapy also significantly reduced the incidence of sensory CIPN, with an RR of 0.67 (95% CI = 0.49 to 0.92). Additionally, cryotherapy demonstrated a significant reduction in the incidence of CIPN in patients with gynecological cancers (RR = 0.24, 95% CI = 0.14 to 0.41). Significantly favorable global quality of life scores following chemotherapy (standardized mean difference = 1.43; 95% CI = 0.50 to 2.36) and relieved neuropathic symptoms were found with cryotherapy.
    CONCLUSIONS: Cryotherapy demonstrates a pronounced preventive effect against the development of CIPN, providing substantial symptomatic relief and quality of life improvements for patients undergoing chemotherapy. The administration of cryotherapy through the use of frozen gloves and socks, or continuous-flow cooling systems, optimally initiated 15 min prior to and concluded 15 min following chemotherapy, is recommended for achieving maximum therapeutic efficacy.
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  • 文章类型: Journal Article
    近年来,非小细胞肺癌(NSCLC)的治疗前景取得了重大进展,标志着向靶向药物和免疫检查点抑制剂(ICIs)的转变。然而,化疗仍然是治疗的基石,单独或组合。微管靶向剂,如紫杉烷和长春花生物碱,在早期和晚期NSCLC的临床实践中起着至关重要的作用。
    这篇综述概述了行动机制,现在的意义,以及微管靶向剂(MTA)的前瞻性进展,在第三阶段试验的新组合上有一个特别的亮点。在线数据库PubMed,WebofScience,科克伦图书馆,和ClinicalTrials.gov使用术语“微管靶向剂”和“非小细胞肺癌”或同义词进行搜索,特别关注过去5年的出版物。
    尽管出现了免疫疗法,MTA仍然至关重要,通常与免疫疗法同时或之后使用,尤其是鳞状细胞肺癌。下一代测序扩展了治疗选择,但是缺乏可靠的免疫疗法生物标志物。虽然抗体-药物缀合物(ADC)显示出希望,管理毒性仍然至关重要。在早期阶段,MTA,可能是ICIs,是标准的,而ADC可能在晚期取代传统化疗。然而,MTA在后续生产线或有禁忌症的患者中仍然是必不可少的。
    UNASSIGNED: The treatment landscape of non-small cell lung cancer (NSCLC) has seen significant advancements in recent years, marked by a shift toward target agents and immune checkpoint inhibitors (ICIs). However, chemotherapy remains a cornerstone of treatment, alone or in combination. Microtubule-targeting agents, such as taxanes and vinca alkaloids, play a crucial role in clinical practice in both early and advanced settings in NSCLC.
    UNASSIGNED: This review outlines the mechanisms of action, present significance, and prospective advancements of microtubule-targeting agents (MTAs), with a special highlight on new combinations in phase 3 trials. The online databases PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched using the terms \'Microtubule-targeting agents\' and \'non-small cell lung cancer\' or synonyms, with a special focus over the last 5 years of publications.
    UNASSIGNED: Despite the emergence of immunotherapy, MTA remains crucial, often used alongside or after immunotherapy, especially in squamous cell lung cancer. Next-generation sequencing expands treatment options, but reliable biomarkers for immunotherapy are lacking. While antibody-drug conjugates (ADCs) show promise, managing toxicities remain vital. In the early stages, MTAs, possibly with ICIs, are standard, while ADCs may replace traditional chemotherapy in the advanced stages. Nevertheless, MTAs remain essential in subsequent lines or for patients with contraindications.
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  • 文章类型: Journal Article
    紫杉烷类是一类具有重要生物活性的二萜,例如紫杉醇(taxol®)是一种优良的天然广谱抗癌药物。生物合成紫杉烷的尝试取得了有限的成功,主要是由于效率低的催化元件的瓶颈。在这项研究中,我们开发了一种人工合成系统,通过生物和化学耦合方法从甲羟戊酸(MVA)生产紫杉烷,它包括体外多酶催化模块,化学催化模块和酵母细胞催化模块。通过优化体外多酶催化体系,在8h内,紫杉二烯的产量从MVA增加到946.7mg/L,生产率比微生物发酵高14.2倍。通过引入钯催化,Taxa-4(20)的转化率,11(12)-二烯-5α-乙酸酯(T5α-AC)达到48%,有效解决了T5αOH产品混杂和产率低的问题。最后,我们优化了T10βOH在酵母中的表达,导致Taxa-4的生物合成(20),11(12)-二烯-5α-乙酰氧基-10β-醇(T5α-AC-10β-醇),产量为15.8mg/L,比共培养发酵策略产生的高2000倍以上。这些技术为紫杉烷的有效合成提供了一种有前途的新方法。
    Taxanes are kinds of diterpenoids with important bioactivities, such as paclitaxel (taxol®) is an excellent natural broad-spectrum anticancer drug. Attempts to biosynthesize taxanes have made with limited success, mainly due to the bottleneck of the low efficiency catalytic elements. In this study, we developed an artificial synthetic system to produce taxanes from mevalonate (MVA) by coupling biological and chemical methods, which comprises in vitro multi-enzyme catalytic module, chemical catalytic module and yeast cell catalytic module. Through optimizing in vitro multienzyme catalytic system, the yield of taxadiene was increased to 946.7 mg/L from MVA within 8 h and the productivity was 14.2-fold higher than microbial fermentation. By incorporating palladium catalysis, the conversion rate of Taxa-4(20),11(12)-dien-5α-yl acetate (T5α-AC) reached 48 %, effectively addressing the product promiscuity and the low yield rate of T5αOH. Finally, we optimized the expression of T10βOH in yeast resulting in the biosynthesis of Taxa-4(20),11(12)-dien-5α-acetoxy-10β-ol(T5α-AC-10β-ol) at a production of 15.8 mg/L, which displayed more than 2000-fold higher than that produced by co-culture fermentation strategy. These technologies offered a promising new approach for efficient synthesis of taxanes.
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  • 文章类型: Journal Article
    Alternariaalternata真菌是一种从Corylusavellana中分离出的有效的紫杉醇生产者。主要挑战是缺乏用于内生真菌生产力的优化培养基。为了使A.alternata最大限度地生产紫杉烷,几种发酵条件,包括pH(pH4.0-7.0),不同类型和浓度的碳(果糖,葡萄糖,蔗糖,甘露醇,山梨醇,和麦芽提取物),和氮(尿素,硝酸铵,硝酸钾,磷酸铵,和硫酸铵)逐步应用。根据结果,A.alternata在含有蔗糖5%(w/v)和2.5mM磷酸铵在pH6.0的培养基中显示出快速和可持续的生长速率,紫杉醇产量最高(94.8µggFW-1与对照中的2.8µggFW-1),和氨基酸的最大含量。此外,果胶对真菌的影响进行了评估,和收获的菌丝体。在第21天,果胶显着提高了生长和紫杉烷产量(分别为第7天相应的171%和116%)。结果也通过数学建模进行检验。因此,这些发现表明低成本,环保,和易于生产的方法,具有优异的生物技术潜力,用于工业制造紫杉烷。
    Alternaria alternata fungus is a potent paclitaxel producer isolated from Corylus avellana. The major challenge is the lack of optimized media for endophytic fungi productivity. In the effort to maximize the production of taxoids by A. alternata, several fermentation conditions, including pH (pH 4.0-7.0), different types and concentrations of carbon (fructose, glucose, sucrose, mannitol, sorbitol, and malt extract), and nitrogen (urea, ammonium nitrate, potassium nitrate, ammonium phosphate, and ammonium sulfate) were applied step by step. Based on the results, A. alternata in a medium containing sucrose 5% (w/v) and ammonium phosphate 2.5 mM at pH 6.0 showed a rapid and sustainable growth rate, the highest paclitaxel yield (94.8 µg gFW-1 vs 2.8 µg gFW-1 in controls), and the maximum content of amino acids. Additionally, the effect of pectin was evaluated on fungus, and mycelia harvested. Pectin significantly enhanced the growth and taxoid yield on day 21 (respectively 171% and 116% of their corresponding on day 7). The results were checked out by mathematical modeling as well. Accordingly, these findings suggest a low-cost, eco-friendly, and easy-to-produce approach with excellent biotechnological potential for the industrial manufacture of taxoids.
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