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Science 9 June 1995:
Vol. 268. no. 5216, pp. 1487 - 1489
DOI: 10.1126/science.7770773
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Articles

Science, Vol 268, Issue 5216, 1487-1489
Copyright © 1995 by American Association for the Advancement of Science

articles

Repositioning of a domain in a modular polyketide synthase to promote specific chain cleavage

J Cortes, KE Wiesmann, GA Roberts, MJ Brown, J Staunton, and PF Leadlay

Cambridge Centre for Molecular Recognition, University of Cambridge, UK.

Macrocyclic polyketides exhibit an impressive range of medically useful activities, and there is great interest in manipulating the genes that govern their synthesis. The 6-deoxyerythronolide B synthase (DEBS) of Saccharopolyspora erythraea, which synthesizes the aglycone core of the antibiotic erythromycin A, has been modified by repositioning of a chain-terminating cyclase domain to the carboxyl-terminus of DEBS1, the multienzyme that catalyzes the first two rounds of polyketide chain extension. The resulting mutant markedly accelerates formation of the predicted triketide lactone, compared to a control in which the repositioned domain is inactive. Repositioning of the cyclase should be generally useful for redirecting polyketide synthesis to obtain polyketides of specified chain lengths.


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