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Science 5 April 1991:
Vol. 252. no. 5002, pp. 114 - 117
DOI: 10.1126/science.2011746
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Articles

Science, Vol 252, Issue 5002, 114-117
Copyright © 1991 by American Association for the Advancement of Science

articles

An erythromycin derivative produced by targeted gene disruption in Saccharopolyspora erythraea

JM Weber, JO Leung, SJ Swanson, KB Idler, and JB McAlpine

BioProcess Development, Department 451/R5, Abbott Laboratories, North Chicago, IL 60064.

Derivatives of erythromycin with modifications at their C-6 position are generally sought for their increased stability at acid pH, which in turn may confer improved pharmacological properties. A recombinant mutant of the erythromycin-producing bacterium, Saccharopolyspora erythraea, produced an erythromycin derivative, 6-deoxyerythromycin A, that could not be obtained readily by chemical synthesis. This product resulted from targeted disruption of the gene, designated eryF (systematic nomenclature, CYP107), that apparently codes for the cytochrome P450, 6-deoxyerythronolide B (DEB) hydroxylase, which converts DEB to erythronolide B (EB). Enzymes normally acting on EB can process the alternative substrate DEB to form the biologically active erythromycin derivative lacking the C-6 hydroxyl group.


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