Borrelidin B: isolation, biological activity, and implications for nitrile biosynthesis.
Borrelidin B: isolation, biological activity, and implications for nitrile biosynthesis.
复制标题
DOI：
10.1021/np500727g
复制
发表时间：
2014-11
影响因子：
5.1
通讯作者：
C. Schulze;Walter M. Bray;F. Loganzo;M. Lam;Teresa Szal;A. Villalobos;F. Koehn;Roger G. Linington
中科院分区：
文献类型：
--
作者：
C. Schulze;Walter M. Bray;F. Loganzo;M. Lam;Teresa Szal;A. Villalobos;F. Koehn;Roger G. Linington
冬凌草素(1)是一种含腈的细菌衍生聚酮，是细菌和真核细胞苏氨酰-tRNA合成酶的有效抑制剂。我们现在报告发现了一种四氢四氢硼烷基衍生物B(2)，它含有一个氨甲基取代了螺纹菌素中的腈官能团。这种新代谢物的发现对丁腈基团的生物合成和钻井素类化合物的生物活性都具有重要意义。在停止试验中对tRNA合成酶抑制进行的筛选表明，腈部分是活性所必需的，而使用我们内部基于图像的细胞学图谱分析表明，2通过引起有丝分裂停滞保持生物活性，即使在没有腈基序的情况下也是如此。
Borrelidin (1) is a nitrile-containing bacterially derived polyketide that is a potent inhibitor of bacterial and eukaryotic threonyl-tRNA synthetases. We now report the discovery of borrelidin B (2), a tetrahydro-borrelidin derivative containing an aminomethyl group in place of the nitrile functionality in borrelidin. The discovery of this new metabolite has implications for both the biosynthesis of the nitrile group and the bioactivity of the borrelidin compound class. Screening in the SToPS assay for tRNA synthetase inhibition revealed that the nitrile moiety is essential for activity, while profiling using our in-house image-based cytological profiling assay demonstrated that 2 retains biological activity by causing a mitotic stall, even in the absence of the nitrile motif.