Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 134, Issue 42, Pages 17444-17447Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja308371z
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Funding
- NIH [GM20011, GM49338, GM092217]
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Members of the asperlicin family of fungal metabolites produced by Aspergillus alliaceus are known potent CCKA antagonists. Herein, we report the identification of the gene cluster responsible for directing their biosynthesis. We validate and probe the pathway by genetic manipulation, and provide the first biochemical characterization of the oxidative cyclization en route to the heptacyclic asperlicin E by reconstituting the activity of the FAD depend monooxygenase AspB. This report provides the first genetic characterization of a NRPS assembly line that efficiently activates two anthranilate building blocks and illustrates the remarkably efficient biosynthesis of the complex heptacyclic asperlicin E.
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