Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany.
Science. 2012 Oct 19;338(6105):387-90. doi: 10.1126/science.1226121. Epub 2012 Sep 13.
It is held as a paradigm that ribosomally synthesized peptides and proteins contain only l-amino acids. We demonstrate a ribosomal origin of the marine sponge-derived polytheonamides, exceptionally potent, giant natural-product toxins. Isolation of the biosynthetic genes from the sponge metagenome revealed a bacterial gene architecture. Only six candidate enzymes were identified for 48 posttranslational modifications, including 18 epimerizations and 17 methylations of nonactivated carbon centers. Three enzymes were functionally validated, which showed that a radical S-adenosylmethionine enzyme is responsible for the unidirectional epimerization of multiple and different amino acids. Collectively, these complex alterations create toxins that function as unimolecular minimalistic ion channels with near-femtomolar activity. This study broadens the biosynthetic scope of ribosomal systems and creates new opportunities for peptide and protein bioengineering.
人们一直认为核糖体合成的肽和蛋白质只含有 L-氨基酸。我们证明了海洋海绵衍生的聚多氨酸的核糖体起源，这些天然产物毒素具有非常强的效力。从海绵宏基因组中分离出生物合成基因，揭示了细菌基因结构。对于 48 种翻译后修饰，只鉴定出 6 种候选酶，包括 18 种消旋和 17 种非活性碳中心的甲基化。三种酶的功能得到了验证，表明一种自由基 S-腺苷甲硫氨酸酶负责多个不同氨基酸的单向消旋。总的来说，这些复杂的变化创造了作为单分子最简离子通道的毒素，其活性接近皮摩尔。这项研究拓宽了核糖体系统的生物合成范围，并为肽和蛋白质的生物工程创造了新的机会。
