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Science 16 April 1999:
Vol. 284. no. 5413, pp. 482 - 485
DOI: 10.1126/science.284.5413.482
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Reports

Dissecting and Exploiting Intermodular Communication in Polyketide Synthases

Rajesh S. Gokhale, 1 Stuart Y. Tsuji, 1 David E. Cane, 4 Chaitan Khosla 123*

Modular polyketide synthases catalyze the biosynthesis of medicinally important natural products through an assembly-line mechanism. Although these megasynthases display very precise overall selectivity, we show that their constituent modules are remarkably tolerant toward diverse incoming acyl chains. By appropriate engineering of linkers, which exist within and between polypeptides, it is possible to exploit this tolerance to facilitate the transfer of biosynthetic intermediates between unnaturally linked modules. This protein engineering strategy also provides insights into the evolution of modular polyketide synthases.

1 Department of Chemical Engineering,
2 Department of Chemistry,
3 Department of Biochemistry, Stanford University, Stanford CA 94305-5025, USA.
4 Department of Chemistry, Brown University, Box H, Providence RI 02912-9108, USA.
*   To whom correspondence should be addressed.

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