Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 54, Issue 6, Pages 1817-1821Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201410219
Keywords
biosynthesis; ketosynthases; mass spectrometry; polyketides; polyketide synthases
Categories
Funding
- Leverhulme Trust [RPG-2012-578]
- Biotechnology and Biological Science Research Council (BBSRC)
- DFG [PI 430/8-1]
- EU (BlueGenics)
- Biotechnology and Biological Sciences Research Council [979707] Funding Source: researchfish
Ask authors/readers for more resources
TypeI modular polyketide synthases (PKSs), which are responsible for the biosynthesis of many biologically active agents, possess a ketosynthase (KS) domain within each module to catalyze chain elongation. Acylation of the KS active site Cys residue is followed by transfer to malonyl-ACP to yield an extended -ketoacyl chain (ACP=acyl carrier protein). To date, the precise contribution of KS selectivity in controlling product fidelity has been unclear. Six KS domains from trans-acyltransferase (trans-AT) PKSs were subjected to a mass spectrometry based elongation assay, and higher substrate selectivity was identified for the elongating step than in preceding acylation. A close correspondence between the observed KS selectivity and that predicted by phylogenetic analysis was seen. These findings provide insights into the mechanism of KS selectivity in this important group of PKSs, can serve as guidance for engineering, and show that targeted mutagenesis can be used to expand the repertoire of acceptable substrates.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available