The calicheamicin gene cluster and its iterative type I enediyne PKS |
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Authors: | Ahlert Joachim Shepard Erica Lomovskaya Natalia Zazopoulos Emmanuel Staffa Alfredo Bachmann Brian O Huang Kexue Fonstein Leonid Czisny Anne Whitwam Ross E Farnet Chris M Thorson Jon S |
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Affiliation: | Laboratory for Biosynthetic Chemistry, Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA. |
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Abstract: | 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. |
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