Aestuaramides, a Natural Library of Cyanobactin Cyclic Peptides Resulting from Isoprene-Derived Claisen Rearrangements

Department of Medicinal Chemistry, College of Pharmacy, University of Utah , Salt Lake City, Utah 84112, United States.
ACS Chemical Biology (Impact Factor: 5.36). 02/2013; 8(5). DOI: 10.1021/cb300614c
Source: PubMed

ABSTRACT We report 12 cyanobactin cyclic peptides, the aestuaramides, from the cultivated cyanobacterium Lyngbya aestuarii. We show that aestuaramides are synthesized enzymatically as reverse O-prenylated tyrosine ethers that subsequently undergo a Claisen rearrangement to produce forward C-prenylated tyrosine. These results reveal that a nonenzymatic Claisen rearrangement dictates isoprene regiochemistry in a natural system. They also reveal one of the mechanisms that organisms use to generate structurally diverse compound libraries starting from simple ribosomal peptide pathways (RiPPs).

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