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烟曲霉 Fresenius,一种来自 Juniperus communis L. Horstmann 的内生真菌,是一种新型抗癌前药脱氧鬼臼毒素的来源。

Aspergillus fumigatus Fresenius, an endophytic fungus from Juniperus communis L. Horstmann as a novel source of the anticancer pro-drug deoxypodophyllotoxin.

机构信息

Institut für Umweltforschung (INFU), Technische Universität Dortmund, Dortmund, Germany.

出版信息

J Appl Microbiol. 2009 Sep;107(3):1019-30. doi: 10.1111/j.1365-2672.2009.04285.x. Epub 2009 Apr 17.

DOI:10.1111/j.1365-2672.2009.04285.x
PMID:19486398
Abstract

AIMS

Isolation, identification and characterization of an endophytic fungus from Juniperus communis L. Horstmann, as a novel producer of deoxypodophyllotoxin and its in vitro antimicrobial assay.

METHODS AND RESULTS

The methodology for the isolation, identification and characterization of a novel endophytic fungus from the twigs of the J. communis L. Horstmann plant, which specifically and consistently produces deoxypodophyllotoxin, was unequivocally established. The fungus was identified as Aspergillus fumigatus Fresenius by molecular, morphological and physiological methods. Deoxypodophyllotoxin was identified and quantified by high-resolution LC-MS, LC-MS(2) and LC-MS(3). The antimicrobial efficacy of the fungal deoxypodophyllotoxin against a panel of pathogenic bacteria was established.

CONCLUSIONS

The production of deoxypodophyllotoxin (found in the host) by the cultured endophyte is an enigmatic observation. It demonstrates the transfer of gene(s) for such accumulation by horizontal means from the host plant to its endophytic counterpart. It would be interesting to further study the deoxypodophyllotoxin production and regulation by the cultured endophyte in J. communis and in axenic cultures.

SIGNIFICANCE AND IMPACT OF THE STUDY

This endophyte is a potential handle for scientific and commercial exploitation. Although the current accumulation of deoxypodophyllotoxin by the endophyte is not very high, it could be scaled-up to provide adequate production to satisfy new drug development and clinical needs. However, further refined precursor-feeding and mass-balance studies are required to result in the consistent and dependable production.

摘要

目的

从 Juniperus communis L. Horstmann 中分离、鉴定和表征一种内生真菌,作为一种新型的脱氧鬼臼毒素的产生菌,并对其进行体外抗菌试验。

方法和结果

明确建立了从 Juniperus communis L. Horstmann 植物嫩枝中分离、鉴定和表征新型内生真菌的方法,该真菌能够特异性和一致性地产生脱氧鬼臼毒素。通过分子、形态和生理方法将真菌鉴定为 Aspergillus fumigatus Fresenius。通过高分辨 LC-MS、LC-MS(2)和 LC-MS(3)鉴定和定量了脱氧鬼臼毒素。确定了真菌脱氧鬼臼毒素对一系列病原菌的抗菌功效。

结论

培养的内生真菌产生脱氧鬼臼毒素(在宿主中发现)是一个神秘的观察结果。它表明,通过水平方式从宿主植物向其内生对应物转移了此类积累的基因(s)。进一步研究培养的 Juniperus communis 内生真菌和无菌培养物中脱氧鬼臼毒素的产生和调控将是有趣的。

研究的意义和影响

这种内生真菌是科学和商业开发的潜在手段。尽管目前内生真菌积累的脱氧鬼臼毒素含量不高,但可以扩大规模以提供足够的产量,以满足新药开发和临床需求。然而,需要进一步进行精细的前体喂养和质量平衡研究,以实现一致和可靠的生产。

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