New Aspercryptins, Lipopeptide Natural Products, Revealed by HDAC Inhibition in Aspergillus nidulans
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- 作者：Matthew T. Henke ; Alexandra A. Soukup ; Anthony W. Goering ; Ryan A. McClure ; Regan J. Thomson ; Nancy P. Keller ; Neil L. Kelleher
- 刊名：ACS Chemical Biology
- 出版年：2016
- 出版时间：August 19, 2016
- 年：2016
- 卷：11
- 期：8
- 页码：2117-2123
- 全文大小：453K
- 年卷期：0
- ISSN：1554-8937
文摘
Unlocking the biochemical stores of fungi is key for developing future pharmaceuticals. Through reduced expression of a critical histone deacetylase in Aspergillus nidulans, increases of up to 100-fold were observed in the levels of 15 new aspercryptins, recently described lipopeptides with two noncanonical amino acids derived from octanoic and dodecanoic acids. In addition to two NMR-verified structures, MS/MS networking helped uncover an additional 13 aspercryptins. The aspercryptins break the conventional structural orientation of lipopeptides and appear “backward” when compared to known compounds of this class. We have also confirmed the 14-gene aspercryptin biosynthetic gene cluster, which encodes two fatty acid synthases and several enzymes to convert saturated octanoic and dodecanoic acid to α-amino acids.