Synthetic chain terminators off-load intermediates from a type I polyketide synthase
Tosin, Manuela, Betancor, Lorena, Stephens, E. (Elaine), Li, W. M. Ariel, Spencer, Jonathan B. and Leadlay, P. F.. (2010) Synthetic chain terminators off-load intermediates from a type I polyketide synthase. Chembiochem, Vol.11 (No.4). pp. 539-546. ISSN 1439-4227Full text not available from this repository.
Official URL: http://dx.doi.org/10.1002/cbic.200900772
Modular biocatalysis is responsible for the generation of countless bioactive products and its mining remains a major focus for drug discovery purposes. One of the enduring hurdles is the isolation of biosynthetic intermediates in a readily-analysed form. We prepared a series of nonhydrolysable pantetheine and N-acetyl cysteamine mimics of the natural (methyl)malonyl extender units recruited for polyketide formation. Using these analogues as competitive substrates, we were able to trap and off-load diketide and triketide species directly from an in vitro reconstituted type I polyketide synthase, the 6-deoxyerythronolide B synthase 3 (DEBS3). The putative intermediates, which were extracted in organic solvent and characterised by LC-HR-ESI-MS, are the first of their kind and prove that small-molecule chain terminators can be used as convenient probes of the biosynthetic process.
|Item Type:||Journal Article|
|Subjects:||Q Science > QD Chemistry
Q Science > QP Physiology
|Divisions:||Faculty of Science > Chemistry|
|Library of Congress Subject Headings (LCSH):||Biosynthesis, Polyketides, Intermediates (Chemistry), Enzymes|
|Journal or Publication Title:||Chembiochem|
|Publisher:||Wiley - V C H Verlag GmbH & Co. KGaA|
|Page Range:||pp. 539-546|
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