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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Biosynthesis of the Cyclitol Moiety of Pyralomicin 1a in Nonomuraea spiralis MI178-34F18
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Biosynthesis of the Cyclitol Moiety of Pyralomicin 1a in Nonomuraea spiralis MI178-34F18

机译:诺诺氏螺旋体MI178-34F18中吡咯霉素1a的环糖醇部分的生物合成

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摘要

The biosynthetic pathway leading to the cyclitol moiety of pyralomicin 1a (1) in Nonomuraea spiralis MI178-34F18 has been studied using a series of ~2H-labeled potential precursors. The results demonstrate that 2-epi-5-epi-valiolone (7), a common precursor for acarbose (4) and validamycin A (5) biosynthesis, is an immediate precursor of pyralomicin 1a. 5-epi-Valiolone (8) was also incorporated into 1, albeit less efficiently than 7. Other potential intermediates, such as valiolone (9), valienone (10), valienol (11), 1-epi-valienol (12), 5-epi-valiolol (13), and 1-eip-5-epi-valiolol (14) wee not incorporated into pyralomicin 1a. To explain this surprising observation, it is proposed that either 2-epi-5-epi-valiolone (7) is specifically activated (e.g., to its phosphate) and that the further transformations take place on activated intermediates (which can not be generated directly from their inactivated counterparts), or that the transformation of 7 into 1 involves a substrate-channeling mechanism in which enzyme-bound intermediates are directly transferred from one enzyme active site to the next in a multi-enzyme complex.
机译:已使用一系列〜2H标记的潜在前体研究了导致Nonomuraea spiralis MI178-34F18中吡咯米星1a(1)的环醇部分的生物合成途径。结果表明,2-epi-5-epi-valiolone(7)是阿卡波糖(4)和有效霉素A(5)生物合成的常见前体,是吡咯米星1a的直接前体。 5-epio-Valiolone(8)也掺入了1,尽管效率不如7。其他潜在的中间体,如valiolone(9),valienone(10),valienol(11),1-epi-valienol(12),未将吡咯米星1a掺入5-epi-valiolol(13)和1-eip-5-epi-valiolol(14)。为了解释这一令人惊讶的发现,建议将2-epi-5-epi-valiolone(7)专门激活(例如,使其磷酸化),并在激活的中间体上进行进一步转化(不能直接生成)或7转化为1涉及底物通道机制,其中酶结合的中间体直接从一个酶活性位点转移到多酶复合物中的下一个酶活性位点。

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