Fisher Mark F, Zhang Jingjing, Taylor Nicolas L, Howard Mark J, Berkowitz Oliver, Debowski Aleksandra W, Behsaz Bahar, Whelan James, Pevzner Pavel A, Mylne Joshua S
The University of Western Australia, School of Molecular Sciences, 35 Stirling Highway, Crawley, Perth 6009, Australia.
ARC Centre of Excellence in Plant Energy Biology, The University of Western Australia, 35 Stirling Highway, Crawley, Perth 6009, Australia.
Plant Direct. 2018 Feb;2(2). doi: 10.1002/pld3.42. Epub 2018 Feb 28.
Orbitides are cyclic ribosomally-synthesized and post-translationally modified peptides (RiPPs) from plants; they consist of standard amino acids arranged in an unbroken chain of peptide bonds. These cyclic peptides are stable and range in size and topologies making them potential scaffolds for peptide drugs; some display valuable biological activities. Recently two orbitides whose sequences were buried in those of seed storage albumin precursors were said to represent the first observable step in the evolution of larger and hydrophilic bicyclic peptides. Here, guided by transcriptome data, we investigated peptide extracts of 40 species specifically for the more hydrophobic orbitides and confirmed 44 peptides by tandem mass spectrometry, as well as obtaining solution structures for four of them by NMR. Acquiring transcriptomes from the phylogenetically important Corymboideae family confirmed the precursor genes for the peptides (called or ) are confined to the Asteroideae, a subfamily of the huge plant family Asteraceae. To be confined to the Asteroideae indicates these peptides arose during the Eocene epoch around 45 Mya. Unlike other orbitides, all PawL-derived Peptides contain an Asp residue, needed for processing by asparaginyl endopeptidase. This study has revealed what is likely to be a very large new family of orbitides, uniquely buried alongside albumin and processed by asparaginyl endopeptidase.
环肽是植物中通过核糖体合成并经翻译后修饰的环状肽（RiPPs）；它们由标准氨基酸组成，通过不间断的肽键链排列。这些环肽稳定，大小和拓扑结构各异，使其成为肽类药物的潜在支架；有些还具有有价值的生物活性。最近，有两种序列隐藏在种子储存白蛋白前体序列中的环肽被认为代表了更大且亲水的双环肽进化过程中第一个可观察到的步骤。在此，我们以转录组数据为指导，专门研究了40种植物的肽提取物中的疏水性更强的环肽，通过串联质谱法确认了44种肽，并通过核磁共振获得了其中4种肽的溶液结构。从系统发育上重要的山茱萸科获取转录组证实，这些肽（称为 或 ）的前体基因仅限于菊科庞大植物家族的一个亚科——紫菀亚科。仅限于紫菀亚科表明这些肽出现在始新世时期，约4500万年前。与其他环肽不同，所有源自PawL的肽都含有一个天冬酰胺内肽酶加工所需的天冬氨酸残基。这项研究揭示了一个可能非常庞大的新环肽家族，它们独特地与白蛋白一起隐藏，并由天冬酰胺内肽酶加工。
