生物技术通报 ›› 2026, Vol. 42 ›› Issue (8): 22-34.doi: 10.13560/j.cnki.biotech.bull.1985.2025-1272
龙俊杰1, 何瑞茜1, 倪子富1, 张敏1, 齐艳利1(
), 李成伟1,2(
)
收稿日期:2025-11-21
出版日期:2026-08-26
发布日期:2026-08-17
通讯作者:
齐艳利yliqi2021@haut.edu.cn基金资助:
LONG Jun-jie1, HE Rui-xi1, NI Zi-fu1, ZHANG Min1, QI Yan-li1(
), LI Cheng-wei1,2(
)
Received:2025-11-21
Published:2026-08-26
Online:2026-08-17
摘要:
紫杉醇是一种高效的四环二萜类抗肿瘤药物,广泛应用于卵巢癌、乳腺癌等多种肿瘤的临床治疗,其传统生产方式依赖红豆杉属植物提取,面临资源短缺与生态风险双重制约。植物内生真菌作为紫杉醇合成的替代来源,展现出可持续生产与工业化应用的潜力。本文系统论述植物内生真菌产紫杉醇的研究进展。从分离来源分析,产紫杉醇内生真菌已从裸子植物(如红豆杉)、被子植物(如欧洲榛)及草本植物(如艾蒿)等多种宿主植物中分离;从微生物分类看,已报道的产紫杉醇内生真菌至少涵盖链格孢霉属(Alternaria)、曲霉属(Aspergillus)、青霉属(Penicillium)等15个真菌类群。野生型菌株的紫杉醇合成能力存在显著差异,产量水平跨度较大(μg/L-mg/L级)。由于培养条件的异质性及缺乏统一的定量检测标准,目前尚未能明确界定具有显著优势的高产菌株。从遗传层面分析,植物紫杉醇合成途径中的部分关键基因在产紫杉醇内生真菌中已鉴定出同源序列,但内生真菌中完整的紫杉醇合成途径尚未被完全解析。当前主要通过菌株筛选、诱变育种及基因编辑等手段对内生真菌底盘细胞进行强化;与此同时,发酵工艺优化、代谢调控与共培养等策略在提升内生真菌紫杉醇产量方面也展现出显著的应用潜力。在合成生物学蓬勃发展的背景下,本文提出今后应加强内生真菌多组学整合分析、合成生物学工具开发和代谢工程等方面研究,旨在为以真菌为底盘的紫杉醇工业化生产提供理论依据和技术支撑。
龙俊杰, 何瑞茜, 倪子富, 张敏, 齐艳利, 李成伟. 植物内生真菌产紫杉醇:研究进展与发展前景[J]. 生物技术通报, 2026, 42(8): 22-34.
LONG Jun-jie, HE Rui-xi, NI Zi-fu, ZHANG Min, QI Yan-li, LI Cheng-wei. Paclitaxel Production by Endophytic Fungi in Plants: Research Advances and Prospects[J]. Biotechnology Bulletin, 2026, 42(8): 22-34.
| 来源 Source | 参考文献 References |
|---|---|
| 红豆杉属 Taxus spp. | [ |
小叶罗汉松 Podocarpus pilgeri 细叶罗汉松 P. gracilior | [ [ |
| 艾蒿 Artemisia judaica | [ |
| 印度紫檀 Terminalia arjuna | [ |
| 辣木 Moringa oleifera | [ |
| 长蒴黄麻 Corchorus olitorius | [ |
| 欧洲榛 Corylus avellana | [ |
| 棕榈 Trachycarpus | [ |
| 木橘 Aegle marmelos | [ |
| 诺丽果树 Morinda citrifolia | [ |
| 银杏 Ginkgo biloba | [ |
| 落叶松 Larix leptolepis | [ |
| 香橼 Citrus medica | [ |
| 朱槿 Hibiscus rosa-sinensis | [ |
| 马松子 Melochia corchorifolia | [ |
表1 部分已报道的产紫杉醇内生真菌的植物宿主
Table 1 Reported plant hosts of paclitaxel-producing endophytic fungi
| 来源 Source | 参考文献 References |
|---|---|
| 红豆杉属 Taxus spp. | [ |
小叶罗汉松 Podocarpus pilgeri 细叶罗汉松 P. gracilior | [ [ |
| 艾蒿 Artemisia judaica | [ |
| 印度紫檀 Terminalia arjuna | [ |
| 辣木 Moringa oleifera | [ |
| 长蒴黄麻 Corchorus olitorius | [ |
| 欧洲榛 Corylus avellana | [ |
| 棕榈 Trachycarpus | [ |
| 木橘 Aegle marmelos | [ |
| 诺丽果树 Morinda citrifolia | [ |
| 银杏 Ginkgo biloba | [ |
| 落叶松 Larix leptolepis | [ |
| 香橼 Citrus medica | [ |
| 朱槿 Hibiscus rosa-sinensis | [ |
| 马松子 Melochia corchorifolia | [ |
内生真菌 Endophytic fungi | 产量 Yield | 参考文献References |
|---|---|---|
| 曲霉 Aspergillus sp. | 432 μg/L | [ |
| 110.2 μg/L | [ | |
| 560 μg/L | [ | |
| 334.2 μg/L | [ | |
| 1 137.6 μg/L | [ | |
| 链格孢 Alternaria sp. | 140.8 μg/L | [ |
| 195.4 μg/L | [ | |
| 124.3 μg/L | [ | |
| 环纹炭团菌 Annulohypoxylon sp. | 282 μg/L | [ |
| 担子菌 Basidiomycete sp. | 382.2 μg/L | [ |
| 7.5 mg/L | [ | |
| 枝孢霉 Cladosporium sp. | 550 μg/L | [ |
| 毛壳菌 Chaetomium sp. | 77.2 μg/L | [ |
| 附球菌 Epicoccum sp. | 1 364.6 μg/L | [ |
| 1.32-1.75 μg/L | [ | |
| 镰孢菌 Fusarium sp. | 0.0153 mg/L | [ |
| 18.2 μg/L | [ | |
| 粘帚霉 Gliocladium sp. | 10.7 μg/L | [ |
| 二孢菌 Lasiodiplodia sp. | 245 μg/L | [ |
| 毛霉 Mucor sp. | 195.1 mg/L | [ |
| 假双球孢菌 Pseudodidymocyrtis sp. | 0.361 mg/g | [ |
| 茎点霉 Phoma sp. | 1.215 mg/L | [ |
| 拟盘多毛孢菌 Pestalotiopsis sp. | 64 μg/L | [ |
| 叶点霉 Phyllosticta sp. | 274 μg/L | [ |
表2 代表性内生真菌的物种分类及紫杉醇产量
Table 2 Taxonomic classification of representative endophytic fungi and their paclitaxel yield
内生真菌 Endophytic fungi | 产量 Yield | 参考文献References |
|---|---|---|
| 曲霉 Aspergillus sp. | 432 μg/L | [ |
| 110.2 μg/L | [ | |
| 560 μg/L | [ | |
| 334.2 μg/L | [ | |
| 1 137.6 μg/L | [ | |
| 链格孢 Alternaria sp. | 140.8 μg/L | [ |
| 195.4 μg/L | [ | |
| 124.3 μg/L | [ | |
| 环纹炭团菌 Annulohypoxylon sp. | 282 μg/L | [ |
| 担子菌 Basidiomycete sp. | 382.2 μg/L | [ |
| 7.5 mg/L | [ | |
| 枝孢霉 Cladosporium sp. | 550 μg/L | [ |
| 毛壳菌 Chaetomium sp. | 77.2 μg/L | [ |
| 附球菌 Epicoccum sp. | 1 364.6 μg/L | [ |
| 1.32-1.75 μg/L | [ | |
| 镰孢菌 Fusarium sp. | 0.0153 mg/L | [ |
| 18.2 μg/L | [ | |
| 粘帚霉 Gliocladium sp. | 10.7 μg/L | [ |
| 二孢菌 Lasiodiplodia sp. | 245 μg/L | [ |
| 毛霉 Mucor sp. | 195.1 mg/L | [ |
| 假双球孢菌 Pseudodidymocyrtis sp. | 0.361 mg/g | [ |
| 茎点霉 Phoma sp. | 1.215 mg/L | [ |
| 拟盘多毛孢菌 Pestalotiopsis sp. | 64 μg/L | [ |
| 叶点霉 Phyllosticta sp. | 274 μg/L | [ |
图1 紫杉醇生物合成通路示意图紫杉醇生物合成途径关键酶:(1)核心骨架合成酶:IDI, GGPPS, TS;(2)核心骨架修饰酶:多位点羟基化酶(T5αH, T10βH, T13αH, T9αH, T7βH, T2αH, T1βH, T2′OGD)与酰基转移酶(TAT, TBT, DBAT);(3)侧链合成与组装酶:PAM, BAPT, T3’DBT。红豆杉属内生真菌紫杉醇生物合成途径中羟化酶、乙酰转移酶和苯甲酰化的相关基因还有待阐明(用蓝色标记)
Fig. 1 Schematic diagram of paclitaxel biosynthetic pathwayThe key enzymes involved in the paclitaxel biosynthetic pathway include: 1) core skeleton synthases: IDI, GGPPS, TS; 2) core skeleton-modifying enzymes: multi-site hydroxylases (T5αH, T10βH, T13αH, T9αH, T7βH, T2αH, T1βH, T2'OGD) and acyltransferases (TAT, TBT, DBAT); 3) side-chain synthesis and assembly enzymes: PAM, BAPT, T3'DBT. The genes related to hydroxylases, acetyltransferases, and benzoylation in the paclitaxel biosynthesis pathway of endophytic fungi of the genus Taxus remain to be elucidated (marked in blue)
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