A Novel Erythromycin, 6-Desmethyl Erythromycin D, Made by Substituting an Acyltransferase Domain of the Erythromycin Polyketide Synthase
نویسندگان
چکیده
منابع مشابه
A 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 کاملAcyltransferase 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 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 کاملIsolation and characterization of 7-hydroxy-6-demethyl-6-deoxy-erythromycin D, a new erythromycin analogue, from engineered Saccharopolyspora erythraea.
Erythromycin biosynthesis is mediated by a modular polyketide synthase (PKS).1,2) Such PKSs feature a separate enzyme active site, as part of discrete protein domains for each biosynthetic step catalyzed, making them ideal targets for directed biosynthesis. Alteration or replacement of individual domains or modules has allowed many new polyketides to be generated with modifications at positions...
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ژورنال
عنوان ژورنال: The Journal of Antibiotics
سال: 2003
ISSN: 0021-8820,1881-1469
DOI: 10.7164/antibiotics.56.543