Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, USA.
J Am Chem Soc. 2012 Jun 27;134(25):10313-6. doi: 10.1021/ja302820x. Epub 2012 Jun 15.
The thiocillins from Bacillus cereus ATCC 14579 are natural products from the broader class of thiazolyl peptides. Their biosynthesis proceeds via extensive post-translational modification of a ribosomally encoded precursor peptide. This post-translational tailoring involves a key step formal cycloaddition between two distal serine residues. In the wild-type structure, this cycloaddition forms a major macrocycle circumscribed by 26-atoms (shortest path). Results presented herein demonstrate the promiscuity of this last step by means of a set of "competition" experiments. Cyclization proceeds in many cases to provide altered ring sizes, giving access to several variant rings sizes that have not previously been observed in nature.
来自蜡状芽孢杆菌 ATCC 14579 的硫霉素是噻唑肽这一更大类别的天然产物。它们的生物合成是通过核糖体编码前体肽的广泛翻译后修饰进行的。这种翻译后修饰涉及两个远端丝氨酸残基之间关键的环加成反应。在野生型结构中，该环加成反应形成一个由 26 个原子（最短路径）界定的大环。本文介绍的结果通过一组“竞争”实验证明了最后一步的混杂性。在许多情况下，环化反应会导致环大小的改变，从而获得几种以前在自然界中未观察到的变体环大小。
