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• W2149783432 startingPage "7305" @default.
• W2149783432 abstract "A previously unknown chemical structure, 6-desmethyl-6-ethylerythromycin A (6-ethylErA), was produced through directed genetic manipulation of the erythromycin (Er)-producing organism Saccharopolyspora erythraea . In an attempt to replace the methyl side chain at the C-6 position of the Er polyketide backbone with an ethyl moiety, the methylmalonate-specific acyltransferase (AT) domain of the Er polyketide synthase was replaced with an ethylmalonate-specific AT domain from the polyketide synthase involved in the synthesis of the 16-member macrolide niddamycin. The genetically altered strain was found to produce ErA, however, and not the ethyl-substituted derivative. When the strain was provided with precursors of ethylmalonate, a small quantity of a macrolide with the mass of 6-ethylErA was produced in addition to ErA. Because substrate for the heterologous AT seemed to be limiting, crotonyl-CoA reductase, a primary metabolic enzyme involved in butyryl-CoA production in streptomycetes, was expressed in the strain. The primary macrolide produced by the reengineered strain was 6-ethylErA." @default.
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• W2149783432 date "1998-06-23" @default.
• W2149783432 modified "2023-10-14" @default.
• W2149783432 title "Ethyl-substituted erythromycin derivatives produced by directed metabolic engineering" @default.
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• W2149783432 doi "https://doi.org/10.1073/pnas.95.13.7305" @default.
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• W2149783432 hasPublicationYear "1998" @default.
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