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内生真菌毛栓菌作为鬼臼毒素及相关芳基四氢萘木脂素的新型替代来源。

The endophytic fungus Trametes hirsuta as a novel alternative source of podophyllotoxin and related aryl tetralin lignans.

作者信息

Puri Satish Chandra, Nazir Asiya, Chawla Raman, Arora Rajesh, Riyaz-Ul-Hasan S, Amna Touseef, Ahmed Bilal, Verma Vijeshwar, Singh Shikha, Sagar Ravinder, Sharma Ashok, Kumar Raj, Sharma Rakesh Kumar, Qazi Ghulam Nabi

机构信息

Natural Products Chemistry Division, Regional Research Laboratory (CSIR), Jammu 180001, India.

出版信息

J Biotechnol. 2006 Apr 20;122(4):494-510. doi: 10.1016/j.jbiotec.2005.10.015. Epub 2005 Dec 20.

Abstract

The aryl tetralin lignans are synthesized by Podophyllum sps. and are in great demand worldwide due to their use in synthesis of topoisomerase inhibitors. However, the sustained production of these aryl tetralin lignans requires large-scale harvesting from the natural environments, which has resulted in the plant-endangered status. In view of the difficulties in their total chemical synthesis, cultivation and failure of metabolic engineering approaches, there is a need to search for alternative sources of production of aryl tetralin lignans. We unequivocally established the methodology for isolation, identification, and characterization of a novel fungal endophyte (Trametes hirsuta) that produces aryl tetralin lignans consistently as shown by HPLC, LC-MS, LC/MS-MS and (1)H NMR. The lignans produced by the microorganism are biologically active, and exhibit potent antioxidant, anticancer and radioprotective properties. This strategy promises to improve the production of these therapeutically important compounds at lower costs.

摘要

芳基四氢萘木脂素由鬼臼属植物合成,由于其在拓扑异构酶抑制剂合成中的应用,在全球范围内需求量很大。然而,这些芳基四氢萘木脂素的持续生产需要从自然环境中大规模采集,这导致了该植物濒危的状况。鉴于其全化学合成、栽培以及代谢工程方法的失败存在困难,有必要寻找芳基四氢萘木脂素的替代生产来源。我们明确建立了一种方法,用于分离、鉴定和表征一种新型真菌内生菌(毛栓菌),通过高效液相色谱(HPLC)、液相色谱 - 质谱联用(LC-MS)、液相色谱/质谱 - 质谱联用(LC/MS-MS)和核磁共振氢谱(¹H NMR)显示,该内生菌能持续产生芳基四氢萘木脂素。该微生物产生的木脂素具有生物活性,并表现出强大的抗氧化、抗癌和辐射防护特性。这一策略有望以更低成本提高这些具有重要治疗意义的化合物的产量。

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