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通过优化生长条件来提高葡萄座腔菌中产紫杉醇的产量。

Enhancement of paclitaxel production by Neopestalotiopsis vitis via optimization of growth conditions.

机构信息

Department of Plant Biology, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran.

Department of Biology, Healthcare and the Environment, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.

出版信息

PLoS One. 2024 Oct 15;19(10):e0309325. doi: 10.1371/journal.pone.0309325. eCollection 2024.

Abstract

Accessibility of paclitaxel and other taxoids from natural resources is restricted. Endophytic fungi are novel, rapidly growing resources for producing these compounds. Neopestalotiopsis vitis (N. vitis) has been recently isolated from Corylus avellana, and its ability to produce a variety of taxoids has been detected and confirmed by analytical methods. Simultaneous growth and high production of taxoids by application of different sorts and concentrations of carbon and nitrogen were targeted in the present research. These criteria were assessed in different acidities (pH 4.0-7.0), carbon sources (sucrose, fructose, glucose, mannitol, sorbitol, and malt extract), and nitrogen forms (urea, ammonium nitrate, potassium nitrate, ammonium phosphate, and ammonium sulfate) by testing one parameter at a time approach. The first analysis introduced pH 7.0 as the best acidity of the medium for N. vitis, where the highest paclitaxel yield was generated. Further analysis introduced 3% Malt extract as the best carbon-providing medium. In the next step, the effects of nitrogen forms on the growth rate, paclitaxel yield, alkaloids, and amino acid contents were evaluated. Based on the results of this experiment, 5 mM ammonium sulfate was selected as the best nitrogen source to obtain the maximum biomass and paclitaxel yield. Overall, the results introduce a medium containing 3% (w/v) malt extract and 5 mM ammonium sulfate at pH 7.0 as the best medium in which N. vitis produces the highest paclitaxel yield coincident with rapid and sustainable growth. The findings pave the way for industrial manufacturing of taxoids.

摘要

天然来源的紫杉醇和其他紫杉烷类药物的获取受到限制。内生真菌是生产这些化合物的新兴、快速增长的资源。最近从榛子中分离出了 Neopestalotiopsis vitis(N. vitis),并通过分析方法检测和确认了其产生多种紫杉烷类化合物的能力。本研究旨在通过应用不同种类和浓度的碳源和氮源,实现紫杉烷类化合物的同步生长和高产。在不同的酸度(pH 值 4.0-7.0)、碳源(蔗糖、果糖、葡萄糖、甘露醇、山梨醇和麦芽提取物)和氮源(尿素、硝酸铵、硝酸钾、磷酸铵和硫酸铵)下,通过逐个参数测试的方法评估了这些标准。第一次分析将 pH 值 7.0 确定为 N. vitis 培养基的最佳酸度,在此酸度下产生的紫杉醇产量最高。进一步的分析引入 3%麦芽提取物作为最佳的碳源提供培养基。在下一步中,评估了氮源对生长速率、紫杉醇产量、生物碱和氨基酸含量的影响。根据该实验的结果,选择 5 mM 硫酸铵作为最佳氮源,以获得最大的生物量和紫杉醇产量。总的来说,结果表明,在 pH 值为 7.0 的培养基中,含有 3%(w/v)麦芽提取物和 5 mM 硫酸铵的培养基是 N. vitis 产生最高紫杉醇产量的最佳培养基,同时实现了快速和可持续的生长。这些发现为紫杉烷类药物的工业生产铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc2d/11478870/e7361ed27fd7/pone.0309325.g001.jpg

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