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Science 16 August 2002:
Vol. 297. no. 5584, pp. 1173 - 1176
DOI: 10.1126/science.1072105
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Reports

The Calicheamicin Gene Cluster and Its Iterative Type I Enediyne PKS

Joachim Ahlert,1 Erica Shepard,1 Natalia Lomovskaya,1 Emmanuel Zazopoulos,2 Alfredo Staffa,2 Brian O. Bachmann,2 Kexue Huang,2 Leonid Fonstein,1 Anne Czisny,1 Ross E. Whitwam,1 Chris M. Farnet,2* Jon S. Thorson1*

The enediynes exemplify nature's ingenuity. We have cloned and characterized the biosynthetic locus coding for perhaps the most notorious member of the nonchromoprotein enediyne family, calicheamicin. This gene cluster contains an unusual polyketide synthase (PKS) that is demonstrated to be essential for enediyne biosynthesis. Comparison of the calicheamicin locus with the locus encoding the chromoprotein enediyne C-1027 reveals that the enediyne PKS is highly conserved among these distinct enediyne families. Contrary to previous hypotheses, this suggests that the chromoprotein and nonchromoprotein enediynes are generated by similar biosynthetic pathways.

1 Laboratory for Biosynthetic Chemistry, Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA.
2 Ecopia Biosciences Inc., 7290 Frederick-Banting, Montreal, Quebec, Canada H4S 2A1.
*   To whom correspondence should be addressed. E-mail: farnet{at}ecopiabio.com; jthorson{at}pharmacy.wisc.edu

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