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- Title
The Interplay between a Multifunctional Dehydratase Domain and a C-Methyltransferase Effects Olefin Shift in Ambruticin Biosynthesis.
- Authors
Berkhan, Gesche; Merten, Christian; Holec, Claudia; Hahn, Frank
- Abstract
The olefin shift is an important modification during polyketide biosynthesis. Particularly for type I cis-AT PKS, little information has been gained on the enzymatic mechanisms involved. We present our in vitro investigations on the olefin shift occurring during ambruticin biosynthesis. The unique, multifunctional domain AmbDH4 catalyzes consecutive dehydration, epimerization, and enoyl isomerization. The resulting 3-enethioate is removed from the equilibrium by α-methylation catalyzed by the highly specific C-methyltransferase AmbM. This thermodynamically unfavorable overall process is enabled by the high, concerted substrate specificity of the involved enzymes. AmbDH4 shows close relationship to DH domains and initial mechanistic studies suggest that the olefin shift occurs via a similar proton-shuttling mechanism as previously described for EI domains from trans-AT-PKS.
- Subjects
OLEFINATION reactions; METHYLTRANSFERASES; POLYKETIDES; CHEMICAL synthesis; EPIMERIZATION; ISOMERIZATION
- Publication
Angewandte Chemie International Edition, 2016, Vol 55, Issue 43, p13589
- ISSN
1433-7851
- Publication type
Article
- DOI
10.1002/anie.201607827