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炭疽菌属物种中抗癌药物紫杉醇生产能力的系统分析及其在紫杉醇生产中的应用。

Systematic Analysis of the Anticancer Agent Taxol-Producing Capacity in Colletotrichum Species and Use of the Species for Taxol Production.

作者信息

Choi Jinhee, Park Jae Gyu, Ali Md Sarafat, Choi Seong-Jin, Baek Kwang-Hyun

机构信息

Institute of Biotechnology, Yeungnam University, Gyeongsan 38541, Korea.; Department of Biotechnology, Yeungnam University, Gyeongsan 38541, Korea.

Pohang Center for Evaluation Biomaterials (POCEB), Pohang Technopark Foundation, Pohang 37668, Korea.

出版信息

Mycobiology. 2016 Jun;44(2):105-11. doi: 10.5941/MYCO.2016.44.2.105. Epub 2016 Jun 30.

DOI:10.5941/MYCO.2016.44.2.105
PMID:27433121
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4945537/
Abstract

Paclitaxel (taxol) has long been used as a potent anticancer agent for the treatment of many cancers. Ever since the fungal species Taxomyces andreanae was first shown to produce taxol in 1993, many endophytic fungal species have been recognized as taxol accumulators. In this study, we analyzed the taxol-producing capacity of different Colletotrichum spp. to determine the distribution of a taxol biosynthetic gene within this genus. Distribution of the taxadiene synthase (TS) gene, which cyclizes geranylgeranyl diphosphate to produce taxadiene, was analyzed in 12 Colletotrichum spp., of which 8 were found to contain the unique skeletal core structure of paclitaxel. However, distribution of the gene was not limited to closely related species. The production of taxol by Colletotrichum dematium, which causes pepper anthracnose, depended on the method in which the fungus was stored, with the highest production being in samples stored under mineral oil. Based on its distribution among Colletotrichum spp., the TS gene was either integrated into or deleted from the bacterial genome in a species-specific manner. In addition to their taxol-producing capacity, the simple genome structure and easy gene manipulation of these endophytic fungal species make them valuable resources for identifying genes in the taxol biosynthetic pathway.

摘要

紫杉醇(泰素)长期以来一直被用作一种有效的抗癌药物,用于治疗多种癌症。自1993年首次发现真菌安德列紫杉霉能产生紫杉醇以来,许多内生真菌物种已被确认为紫杉醇积累者。在本研究中,我们分析了不同炭疽菌属物种产生紫杉醇的能力,以确定该属内紫杉醇生物合成基因的分布情况。在12种炭疽菌属物种中分析了紫杉二烯合酶(TS)基因的分布,该基因可将香叶基香叶基二磷酸环化生成紫杉二烯,其中8种被发现含有紫杉醇独特的骨架核心结构。然而,该基因的分布并不局限于亲缘关系密切的物种。引起辣椒炭疽病的盘长孢炭疽菌产生紫杉醇的情况取决于真菌的保存方法,在矿物油下保存的样品中产量最高。基于其在炭疽菌属物种中的分布情况,TS基因以物种特异性方式整合到细菌基因组中或从细菌基因组中缺失。除了它们产生紫杉醇的能力外,这些内生真菌物种简单的基因组结构和易于进行的基因操作使其成为鉴定紫杉醇生物合成途径中基因的宝贵资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24c9/4945537/0ff8772c9e1e/mb-44-105-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24c9/4945537/37ecb83426e5/mb-44-105-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24c9/4945537/9a762d405f8f/mb-44-105-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24c9/4945537/0ff8772c9e1e/mb-44-105-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24c9/4945537/37ecb83426e5/mb-44-105-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24c9/4945537/9a762d405f8f/mb-44-105-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24c9/4945537/0ff8772c9e1e/mb-44-105-g003.jpg

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本文引用的文献

1
Characterization of Colletotrichum Species Responsible for Anthracnose Diseases of Various Fruits.引起多种果实炭疽病的炭疽菌属物种的鉴定
Plant Dis. 1998 Jun;82(6):596-605. doi: 10.1094/PDIS.1998.82.6.596.
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Survival of Colletotrichum dematium in Soil and Infected Mulberry Leaves.炭疽菌在土壤和感染的桑叶中的存活情况。
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Colletotrichum orbiculare Secretes Virulence Effectors to a Biotrophic Interface at the Primary Hyphal Neck via Exocytosis Coupled with SEC22-Mediated Traffic.
产紫杉醇内生真菌枝孢霉MD2的转录组分析
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An endophytic Basidiomycete, Grammothele lineata, isolated from Corchorus olitorius, produces paclitaxel that shows cytotoxicity.从黄麻中分离出的一种内生担子菌——线条粘束孢,能产生具有细胞毒性的紫杉醇。
PLoS One. 2017 Jun 21;12(6):e0178612. doi: 10.1371/journal.pone.0178612. eCollection 2017.
炭疽菌通过与SEC22介导的运输偶联的胞吐作用,将毒力效应蛋白分泌到初生菌丝颈部的活体营养界面。
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An adequate Fe nutritional status of maize suppresses infection and biotrophic growth of Colletotrichum graminicola.玉米充足的铁营养状况可抑制禾谷炭疽菌的感染和活体营养生长。
Physiol Plant. 2014 Jul;151(3):280-92. doi: 10.1111/ppl.12166. Epub 2014 Mar 18.
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MEGA6: Molecular Evolutionary Genetics Analysis version 6.0.MEGA6:分子进化遗传学分析版本 6.0。
Mol Biol Evol. 2013 Dec;30(12):2725-9. doi: 10.1093/molbev/mst197. Epub 2013 Oct 16.
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Occurrence and characterization of Colletotrichum dematium (Fr.) grove.炭疽菌属(Fr.)格罗夫的发生和特征。
Pol J Microbiol. 2010;59(3):191-200.
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A review: recent advances and future prospects of taxol-producing endophytic fungi.综述:紫杉醇产生内生真菌的最新进展和未来前景。
Appl Microbiol Biotechnol. 2010 May;86(6):1707-17. doi: 10.1007/s00253-010-2546-y. Epub 2010 Apr 1.
8
Effect of taxol feeding on taxol and related taxane production in Taxus baccata suspension cultures.紫杉醇投喂对欧洲红豆杉悬浮培养物中紫杉醇及相关紫杉烷产量的影响。
N Biotechnol. 2009 Apr;25(4):252-9. doi: 10.1016/j.nbt.2008.11.001. Epub 2008 Dec 3.
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Evidence for paclitaxel from three new endophytic fungi of Himalayan yew of Nepal.来自尼泊尔喜马拉雅红豆杉三种新内生真菌的紫杉醇证据。
Planta Med. 2001 Jun;67(4):374-6. doi: 10.1055/s-2001-14307.
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Taxol-induced ceramide generation and apoptosis in human breast cancer cells.紫杉醇诱导人乳腺癌细胞中神经酰胺的生成及凋亡。
Cancer Chemother Pharmacol. 2001 May;47(5):444-50. doi: 10.1007/s002800000265.