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Science 15 November 1996:
Vol. 274. no. 5290, pp. 1188 - 1193
DOI: 10.1126/science.274.5290.1188
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Reports

From Peptide Precursors to Oxazole and Thiazole-Containing Peptide Antibiotics: Microcin B17 Synthase

Yue-Ming Li, Jill C. Milne, Lara L. Madison, Roberto Kolter, Christopher T. Walsh *

Esherichia coli microcin B17 is a posttranslationally modified peptide that inhibits bacterial DNA gyrase. It contains four oxazole and four thiazole rings and is representative of a broad class of pharmaceutically important natural products with five-membered heterocycles derived from peptide precursors. An in vitro assay was developed to detect heterocycle formation, and an enzyme complex, microcin B17 synthase, was purified and found to contain three proteins, McbB, McbC, and McbD, that convert 14 residues into the eight mono- and bisheterocyclic moieties in vitro that confer antibiotic activity on mature microcin B17. These enzymatic reactions alter the peptide backbone connectivity. The propeptide region of premicrocin is the major recognition determinant for binding and downstream heterocycle formation by microcin B17 synthase. A general pathway for the enzymatic biosynthesis of these heterocycles is formulated.

Y.-M. Li, J. C. Milne, C. T. Walsh, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
L. L. Madison and R. Kolter, Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
*   To whom correspondence should be addressed.

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