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 t...

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Bibliographic Details
Published in:Journal of antibiotics 2003/06/25, Vol.56(6), pp.543-551
Main Authors: PETKOVIC, HRVOJE, LILL, RACHEL E., SHERIDAN, ROSE M., WILKINSON, BARRIE, McCORMICK, ELLEN L., McARTHUR, HAMISH A. I., STAUNTON, JAMES, LEADLAY, PETER F., KENDREW, STEVEN G.
Format: Article
Language:English
Subjects:
Acyltransferases
Anti-Bacterial Agents - isolation & purification
Anti-Bacterial Agents - metabolism
Anti-Bacterial Agents - pharmacology
Antibiotics
Base Sequence
Biological and medical sciences
Biotechnology
Erythromycin - analogs & derivatives
Erythromycin - isolation & purification
Erythromycin - pharmacology
Fermentation
Fundamental and applied biological sciences. Psychology
Health. Pharmaceutical industry
Industrial applications and implications. Economical aspects
Microbial Sensitivity Tests
Multienzyme Complexes
Production of active biomolecules
Structure-Activity Relationship
Substrate Specificity
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Summary: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 erythromycin PKS and reinforces PKS engineering as a robust and generic tool.
ISSN:0021-8820
1881-1469
DOI:10.7164/antibiotics.56.543