利用全球次级代谢调节因子 laeA 基因分离出抗疟化合物硬骨素 A。

IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL Bioorganic & Medicinal Chemistry Letters Pub Date : 2024-09-07 DOI:10.1016/j.bmcl.2024.129947
Sota Honma , Aoi Kimishima , Satoshi Kato , Akari Horiuchi , Rei Hokari , Masako Honsho , Hiroki Kojima , Toshiyuki Tokiwa , Akihiro Sugawara , Masato Iwatsuki , Yasuko Araki , Tadashi Takahashi , Takumi Chinen , Takeo Usui , Kotaro Ito , Yukihiro Asami
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引用次数: 0

摘要

此前,我们曾成功地将laeA基因导入真菌菌株,从而显著提高了一种生物活性化合物的产量,从而发现了新的生物活性。为了证明laeA基因导入策略在挖掘真菌次生代谢潜力方面的普遍适用性,在本研究中,我们创建了一个插入laeA基因的微生物文库,目的是从该文库中分离出与野生型菌株相比产量明显增加的化合物。通过这项调查,我们从 Pochonia sp. KTF-0504 菌株中分离出了硬菌素 A(1)。我们发现,1 对恶性疟原虫菌株具有抗疟疾活性。另一方面,1 对多种药物敏感的芽生酵母没有抗真菌活性。我们的研究表明,利用真菌中的laeA基因是发现候选药物的一种多用途方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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The isolation of sclerotinin A as an anti-malarial compound by utilization of a global secondary metabolism regulator, laeA gene

Previously, we successfully introduced laeA gene into a fungal strain in order to significantly increase the production of a bioactive compound, allowing use to discover novel biological activity. To demonstrate the universal applicability of the laeA gene introduction strategy for taping the potential of fungal secondary metabolism, in this present study, we created a library of microorganisms which we had the laeA gene inserted, and from that library we aimed to isolate compounds which are produced at significantly greater quantities compared to the respective wild type strains. From this investigation, we were able to isolate sclerotinin A (1) from Pochonia sp. KTF-0504 strain. We revealed that 1 showed anti-malarial activity against Plasmodium falciparum parasite strains. On the other hands, 1 showed no anti-fungal activity against multidrug-sensitive budding yeast. Our study implies that the utilization of the laeA gene in fungi is a versatile method for the discovery of drug candidates.

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来源期刊
CiteScore
5.70
自引率
3.70%
发文量
463
审稿时长
27 days
期刊介绍: Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.
期刊最新文献
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