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果胶诱导后,通过链格孢菌优化发酵培养基、数学建模及紫杉醇生产的增强。

Optimization of the fermentation media, mathematical modeling, and enhancement of paclitaxel production by Alternaria alternata after elicitation with pectin.

机构信息

Department of Plant Biology, Faculty of Biological Sciences, Tarbiat Modares University (TMU), POB 14115-154, Tehran, Iran.

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

出版信息

Sci Rep. 2024 Jun 5;14(1):12980. doi: 10.1038/s41598-024-63681-w.

Abstract

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 vs 2.8 µg gFW 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.

摘要

从榛子中分离出的交替霉菌是一种强效的紫杉醇产生菌。主要的挑战是缺乏优化的内生真菌生产力培养基。为了最大限度地提高交替霉菌的紫杉烷产量,我们逐步应用了几种发酵条件,包括 pH 值(4.0-7.0)、不同类型和浓度的碳源(果糖、葡萄糖、蔗糖、甘露醇、山梨醇和麦芽提取物)以及氮源(尿素、硝酸铵、硝酸钾、磷酸铵和硫酸铵)。基于这些结果,在 pH 值为 6.0、含有 5%(w/v)蔗糖和 2.5 mM 磷酸铵的培养基中,交替霉菌表现出快速而持续的生长速度、最高的紫杉醇产量(94.8 µg gFW 比对照中的 2.8 µg gFW)和最高的氨基酸含量。此外,我们还评估了果胶对真菌和菌丝体的影响。果胶显著提高了第 21 天的生长和紫杉烷产量(分别比第 7 天提高了 171%和 116%)。结果也通过数学建模进行了验证。因此,这些发现表明,对于紫杉烷的工业生产,这是一种具有低成本、环保和易于生产的方法,具有极好的生物技术潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f357/11153502/4e648818a314/41598_2024_63681_Fig1_HTML.jpg

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