生成复杂性的短途径：基于邻氨基苯甲酸构建单元的真菌肽基生物碱多环骨架
Short pathways to complexity generation: fungal peptidyl alkaloid multicyclic scaffolds from anthranilate building blocks.
作者信息
Walsh Christopher T, Haynes Stuart W, Ames Brian D, Gao Xue, Tang Yi
机构信息
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School , 25 Shattuck Street, Boston, Massachusetts.
出版信息
ACS Chem Biol. 2013 Jul 19;8(7):1366-82. doi: 10.1021/cb4001684. Epub 2013 Jun 4.
Abstract
Complexity generation in naturally occurring peptide scaffolds can occur either by posttranslational modifications of nascent ribosomal proteins or through post assembly line tailoring of nonribosomal peptides. Short enzymatic pathways utilizing bimodular and trimodular nonribosomal peptide synthetase (NRPS) assembly lines, followed by tailoring oxygenases and/or prenyltransferases, efficiently construct complex fungal peptidyl alkaloid scaffolds in Aspergilli, Neosartorya, and Penicillium species. Use of the nonproteinogenic amino acid anthranilate as chain-initiating building block and chain-terminating intramolecular nucleophile leads efficiently to peptidyl alkaloid scaffolds with two to seven fused rings.
摘要
天然存在的肽支架中的复杂性生成可以通过新生核糖体蛋白的翻译后修饰或通过非核糖体肽的装配后修饰来实现。利用双模块和三模块非核糖体肽合成酶（NRPS）装配线，随后进行修饰氧化酶和/或异戊烯基转移酶的短酶促途径，可在曲霉属、新萨托菌属和青霉属物种中高效构建复杂的真菌肽基生物碱支架。使用非蛋白质氨基酸邻氨基苯甲酸作为链起始构建块和链终止分子内亲核试剂可有效地生成具有两到七个稠合环的肽基生物碱支架。
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