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Production of Kinanthraquinone D with Antimalarial Activity by Heterologous Gene Expression and Biotransformation in Streptomyces lividans TK23
Journal of Natural Products ( IF 5.1 ) Pub Date : 2024-02-27 , DOI: 10.1021/acs.jnatprod.3c01076
Katsuyuki Sakai 1 , Yushi Futamura 2 , Toshihiko Nogawa 3 , Yuzhu Zhao 1, 4 , Hiroyuki Koshino 3 , Hiroyuki Osada 2 , Shunji Takahashi 1, 4
Affiliation  

Two new compounds, kinanthraquinone C (1) and kinanthraquinone D (2), were isolated along with two known compounds, kinanthraquinone (3) and kinanthraquinone B (4), produced by the heterologous expression of the kiq biosynthetic gene cluster and its pathway-specific regulator, kiqA, in Streptomyces lividans TK23. The chemical structures of compounds 1 and 2 were determined using mass spectrometry and nuclear magnetic resonance analyses. To examine a biosynthetic pathway of compounds 1 and 2, incubation experiments were conducted using S. lividans TK23 to supply the compounds 3 and 4. These experiments indicated that compounds 3 and 4 were converted to compounds 2 and 1, respectively, by the endogenous enzymes of S. lividans TK23. Compounds 2, 3, and 4 had antimalarial activities at half-maximal inhibitory concentration values of 0.91, 1.2, and 15 μM, respectively, without cytotoxicity up to 30 μM.

中文翻译:

通过异源基因表达和生物转化在浅青紫链霉菌 TK23 中生产具有抗疟活性的 Kinanthraquinone D

分离出两种新化合物,kinanthraquinone C ( 1 ) 和kinanthraquinone D ( 2 ),以及两种已知化合物,kinanthraquinone ( 3 ) 和kinanthraquinone B ( 4 ),它们是通过kiq生物合成基因簇及其途径的异源表达产生的 -变青链霉菌TK23中的特异性调节因子kiqA。使用质谱和核磁共振分析确定了化合物12的化学结构。为了检查化合物12的生物合成途径,使用S.lividans TK23进行培养实验以提供化合物34。这些实验表明,化合物34通过变青链球菌TK23的内源酶分别转化为化合物21。化合物2、34在半数抑制浓度值分别为0.91、1.2和15μM时具有抗疟活性,并且在高达30μM时没有细胞毒性
更新日期:2024-02-27
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