Acyltransferase domain substitutions in erythromycin polyketide synthase yield novel erythromycin derivatives
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چکیده
منابع مشابه
Acyltransferase domain substitutions in erythromycin polyketide synthase yield novel erythromycin derivatives.
The methylmalonyl coenzyme A (methylmalonyl-CoA)-specific acyltransferase (AT) domains of modules 1 and 2 of the 6-deoxyerythronolide B synthase (DEBS1) of Saccharopolyspora erythraea ER720 were replaced with three heterologous AT domains that are believed, based on sequence comparisons, to be specific for malonyl-CoA. The three substituted AT domains were "Hyg" AT2 from module 2 of a type I po...
متن کاملA novel erythromycin, 6-desmethyl erythromycin D, made by substituting an acyltransferase domain of the erythromycin polyketide synthase.
The acyltransferase (AT) domain in module 4 of the erythromycin polyketide synthase (PKS) was substituted with an AT domain from the rapamycin PKS module 2 in order to alter the substrate specificity from methylmalonyl-CoA to malonyl-CoA. The resulting strain produced 6-desmethyl erythromycin D as the predominant product. This AT domain swap completes the library of malonyl-CoA AT swaps on the ...
متن کاملProgramming of erythromycin biosynthesis by a modular polyketide synthase.
Since the discovery and sequencing of 6-deoxyerythronolide B synthase 20 years ago, this exceptionally large, multifunctional protein remains the paradigm for the understanding of the structure and biochemical function of modular polyketide synthases. The broad-spectrummacrolide antibiotic erythromycin is one of several hundred closely related, branched chain, polyoxygenated polyketides, many o...
متن کاملMechanism and specificity of the terminal thioesterase domain from the erythromycin polyketide synthase.
BACKGROUND Polyketides are important compounds with antibiotic and anticancer activities. Several modular polyketide synthases (PKSs) contain a terminal thioesterase (TE) domain probably responsible for the release and concomitant cyclization of the fully processed polyketide chain. Because the TE domain influences qualitative aspects of product formation by engineered PKSs, its mechanism and s...
متن کاملEpimerization of erythromycin derivatives.
Dirithromycin (3) isomerizes upon dissolution in different solvents. From X-ray analysis of V-T 108, an analogue of dirithromycin, and comparative 1H and 13C NMR, and MS data, the isomer of dirithromycin was confirmed to be the C-16-(S)-epimer. The ratio of the two epimers at equilibrium conditions was approximately 8:2 (R/S) in methanol at room temperature.
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ژورنال
عنوان ژورنال: Journal of Bacteriology
سال: 1997
ISSN: 0021-9193,1098-5530
DOI: 10.1128/jb.179.20.6416-6425.1997