Short Pathways to Complexity Generation: Fungal Peptidyl Alkaloid Multicyclic Scaffolds from Anthranilate Building Blocks

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• 作者：Christopher T. Walsh ; Stuart W. Haynes ; Brian D. Ames ; Xue Gao ; Yi Tang
• 刊名：ACS Chemical Biology
• 出版年：2013
• 出版时间：July 19, 2013
• 年：2013
• 卷：8
• 期：7
• 页码：1366-1382
• 全文大小：1048K
• 年卷期：v.8,no.7(July 19, 2013)
• ISSN：1554-8937

文摘

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.