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Codon Randomization for Rapid Exploration of Chemical Space in Thiopeptide Antibiotic Variants
Authors:Travis   S. Young,Pieter   C. Dorrestein,Christopher   T. Walsh
Affiliation:1. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Armenise 608, Boston, MA 02115, USA;2. Skaggs School of Pharmacy and Pharmaceutical Sciences, Departments of Pharmacology and Chemistry and Biology, University California, San Diego, 9500 Gilman Drive, MC 0636, La Jolla, CA 92093-0636, USA
Abstract:
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  • Highlights? Thiopeptide GE37468 expression was increased 30-fold above previous reports ? Codon randomization enabled rapid exploration of chemical space ? Thirteen thiopeptide analogs had activity against MRSA ? Identification of linear precursor peptides allowed insights into biosynthetic timing
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