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Covalent linkage mediates communication between ACP and TE domains in modular polyketide synthases
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Tran, Lucky, Tosin, Manuela, Spencer, Jonathan B., Leadlay, P. F. and Weissman, Kira J. (2008) Covalent linkage mediates communication between ACP and TE domains in modular polyketide synthases. Chembiochem, Vol.9 (No.6). pp. 905-915. doi:10.1002/cbic.200700738 ISSN 1439-4227.
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Official URL: http://dx.doi.org/10.1002/cbic.200700738
Abstract
Polyketide natural products such as erythromycin A and epothilone are assembled on multienzyme polyketide synthases (PKSs), which consist of modular sets of protein domains. Within these type I systems, the fidelity of biosynthesis depends on the programmed interaction among the multiple domains within each module, centered around the acyl carrier protein (ACP). A detailed understanding of interdomain communication will therefore be vital for attempts to reprogram these pathways by genetic engineering. We report here that the interaction between a representative ACP domain and its downstream thioesterase (TE) is mediated largely by covalent tethering through a short “linker” region, with only a minor energetic contribution from protein–protein molecular recognition. This finding helps explain in part the empirical observation that TE domains can function out of their normal context in engineered assembly lines, and supports the view that overall PKS architecture may dictate at least a subset of interdomain interactions.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > QD Chemistry Q Science > QP Physiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||
| Library of Congress Subject Headings (LCSH): | Carrier proteins, Polyketides, Biosynthesis | ||||
| Journal or Publication Title: | Chembiochem | ||||
| Publisher: | Wiley - V C H Verlag GmbH & Co. KGaA | ||||
| ISSN: | 1439-4227 | ||||
| Official Date: | 2008 | ||||
| Dates: |
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| Volume: | Vol.9 | ||||
| Number: | No.6 | ||||
| Page Range: | pp. 905-915 | ||||
| DOI: | 10.1002/cbic.200700738 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC) |
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