KOPS - The Institutional Repository of the University of Konstanz

Malonyl carba(dethia)- and Malonyl oxa(dethia)-coenzyme A as Tools for Trapping Polyketide Intermediates

Malonyl carba(dethia)- and Malonyl oxa(dethia)-coenzyme A as Tools for Trapping Polyketide Intermediates

Cite This

Files in this item

Files Size Format View

There are no files associated with this item.

TOSIN, Manuela, Dieter SPITELLER, Jonathan B. SPENCER, 2009. Malonyl carba(dethia)- and Malonyl oxa(dethia)-coenzyme A as Tools for Trapping Polyketide Intermediates. In: ChemBioChem. 10(10), pp. 1714-1723. ISSN 1439-4227. eISSN 1439-7633. Available under: doi: 10.1002/cbic.200900093

@article{Tosin2009-07-06Malon-15298, title={Malonyl carba(dethia)- and Malonyl oxa(dethia)-coenzyme A as Tools for Trapping Polyketide Intermediates}, year={2009}, doi={10.1002/cbic.200900093}, number={10}, volume={10}, issn={1439-4227}, journal={ChemBioChem}, pages={1714--1723}, author={Tosin, Manuela and Spiteller, Dieter and Spencer, Jonathan B.} }

Spencer, Jonathan B. eng 2011-10-19T07:33:45Z Tosin, Manuela Publ. in: ChemBioChem [A European Journal of Chemical Biology] ; 10 (2009), 10. - pp. 1714-1723 Spencer, Jonathan B. Tosin, Manuela Spiteller, Dieter terms-of-use 2009-07-06 2011-10-19T07:33:45Z Caught in a trap. In this study trapped polyketide species (see figure) were off-loaded from a type III PKS by novel nonhydrolyzable malonyl coenzyme A analogues in which a methylene group or an oxygen atom replaces the sulfur atom of malonyl-CoA. This strategy allows the straightforward characterisation of intermediates of polyketide biosynthesis by LC-HR-ESI-MS/MS and provides valuable insights on the mechanism and timing of polyketide formation.<br /><br />In order to study intermediates in polyketide biosynthesis two nonhydrolyzable malonyl coenzyme A analogues were synthesised by a chemoenzymatic route. In these analogues the sulfur atom of CoA was replaced either by a methylene group (carbadethia analogue) or by an oxygen atom (oxadethia analogue). These malonyl-CoA analogues were found to compete with the natural extender unit malonyl-CoA and to trap intermediates from stilbene synthase, a type III polyketide synthase (PKS). From the reaction of stilbene synthase with its natural phenylpropanoid substrates, diketide, triketide and tetraketide species were successfully off-loaded and characterised by LC-MS. Moreover, the reactivity of the nonhydrolyzable analogues offers insights into the flexibility of substrate alignment in the PKS active site for efficient malonyl decarboxylation and condensation. Malonyl carba(dethia)- and Malonyl oxa(dethia)-coenzyme A as Tools for Trapping Polyketide Intermediates Spiteller, Dieter

This item appears in the following Collection(s)

Search KOPS


Browse

My Account