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Science 12 September 2003:
Vol. 301. no. 5639, pp. 1537 - 1541
DOI: 10.1126/science.1086695
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Reports

Resistance to Enediyne Antitumor Antibiotics by CalC Self-Sacrifice

John B. Biggins,1,2 Kenolisa C. Onwueme,2 Jon S. Thorson1,2*

Antibiotic self-resistance mechanisms, which include drug elimination, drug modification, target modification, and drug sequestration, contribute substantially to the growing problem of antibiotic resistance among pathogenic bacteria. Enediynes are among the most potent naturally occurring antibiotics, yet the mechanism of resistance to these toxins has remained a mystery. We characterize an enediyne self-resistance protein that reveals a self-sacrificing paradigm for resistance to highly reactive antibiotics, and thus another opportunity for nonpathogenic or pathogenic bacteria to evade extremely potent small molecules.

1 Laboratory for Biosynthetic Chemistry, Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin–Madison, 777 Highland Avenue, Madison, WI 53705, USA.
2 Molecular Pharmacology and Therapeutics Program, The Sloan-Kettering Division, Joan and Sanford I. Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021, USA.

* To whom correspondence should be addressed. E-mail: jsthorson{at}pharmacy.wisc.edu

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