Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 West Gregory Drive, Urbana, Illinois 61801, USA.
J Am Chem Soc. 2016 Dec 7;138(48):15511-15514. doi: 10.1021/jacs.6b08987. Epub 2016 Oct 13.
The biosynthesis of the thiopeptide thiomuracin is a well-orchestrated process involving a multitude of posttranslational modifications. We show that six Cys residues of a precursor peptide are first cyclodehydrated and oxidized to thiazoles in an ordered, but nonlinear fashion that is leader-peptide-dependent. Then four alcohols are glutamylated and converted to alkenes in a C-to-N terminal directional process that is leader-peptide-independent. Finally, two of these alkenes undergo a formal [4 + 2] cycloaddition to form a trithiazole-substituted pyridine macrocycle. We describe here the factors that govern the substrate specificity and order of biosynthetic events that turn a ribosomal peptide into a powerful antibiotic.
硫肽噻霉素的生物合成是一个精心协调的过程，涉及多种翻译后修饰。我们表明，前体肽中的六个半胱氨酸残基首先以有序但非线性的方式环脱水并氧化为噻唑，这依赖于前导肽。然后，四个醇在 C 端到 N 端的定向过程中被谷氨酸化并转化为烯烃，该过程不依赖于前导肽。最后，其中两个烯烃经历一个正式的[4+2]环加成反应，形成一个三噻唑取代的吡啶大环。我们在这里描述了控制生物合成事件底物特异性和顺序的因素，这些因素将核糖体肽转化为一种强大的抗生素。
