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Generation of incednine derivatives by mutasynthesis.
The Journal of Antibiotics ( IF 3.3 ) Pub Date : 2020-06-04 , DOI: 10.1038/s41429-020-0329-y
Akimasa Miyanaga 1 , Ryoma Takaku 1 , Makoto Takaishi 1 , Etsu Tashiro 2 , Fumitaka Kudo 1 , Tadashi Eguchi 1
Affiliation  

The macrolactam antibiotic incednine, isolated from Streptomyces sp. ML694–90F3, contains a (S)-3-aminobutyric acid moiety in its polyketide aglycon. In this study, we performed mutasynthesis to generate incednine derivatives. We successfully obtained 28-methylincednine by feeding 3-aminopentanoic acid into culture of a strain in which the glutamate 2,3-aminomutase gene idnL4, whose product is responsible for supplying 3-aminobutyric acid, was disrupted. 28-Methylincednine showed similar suppressive activity of the antiapoptotic function of oncoprotein Bcl-xL to that of incednine. Thus, this study highlights the applicability of the mutasynthesis approach in generation of novel β-amino acid-containing macrolactam polyketide derivatives.



中文翻译:

通过诱变生成手工艺衍生物。

从内生链霉菌中分离出的大环内酰胺类抗菌素。ML694–90F3在其聚酮化合物糖苷配基中包含(S)-3-氨基丁酸部分。在这项研究中,我们进行了突变合成,以生成手工艺衍生物。我们成功地通过将3-氨基戊酸送入一个菌株的培养物中成功获得了28-甲基茚二碱,在该菌株中,负责提供3-氨基丁酸的谷氨酸2,3-氨基变位酶基因idnL4被破坏。28-甲基亚铁亚胺对癌蛋白Bcl-xL的抗凋亡功能的抑制活性与因西得宁相似。因此,本研究强调了诱变方法在产生新型含β-氨基酸的大内酰胺聚酮化合物衍生物中的适用性。

更新日期:2020-06-04
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