The loading module of mycosubtilin: An adenylation domain with fatty acid selectivity

被引:66
作者
Hansen, Darren B.
Bumpus, Stefanie B.
Aron, Zachary D.
Kelleher, Neil L.
Walsh, Christopher T.
机构
[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
[2] Univ Illinois, Dept Chem, Urbana, IL 61801 USA
关键词
D O I
10.1021/ja070890j
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
We report the cloning and characterization of the loading domain of mycosubtilin A synthetase responsible for the biosynthesis of mycosubtilin, a lipopeptide natural product from Bacillus subtilis. A truncated form of mycA was cloned and overexpressed and found to activate free fatty acids though an acyl-adenylate intermediate and loaded on the adjacent thiolation domain independently of coenzyme A, contradicting the literature proposal that the loading module is a coenzyme A ligase. The activation and loading of free fatty acids was characterized with a combination of traditional biochemical assays and electrospray ionization-Fourier transform mass spectrometry.
引用
收藏
页码:6366 / +
页数:3
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