核糖体蛋白
基因组
计算生物学
蛋白质组学
核糖体
蛋白质组
作者
Michael F. Freeman,Cristian Gurgui,Maximilian J. Helf,Brandon I. Morinaka,Agustinus Robert Uria,Neil J. Oldham,Hans-Georg Sahl,Shigeki Matsunaga,Jörn Piel
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2012-10-19
卷期号:338 (6105): 387-390
被引量:225
标识
DOI:10.1126/science.1226121
摘要
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.
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