Article
A Single Active Site Mutation in the Pikromycin Thioesterase Generates a More Effective Macrocyclization Catalyst.
Journal of the American Chemical Society - 27 Sept 2017
Koch Aaron A, Hansen Douglas A, Shende Vikram V, Furan Lawrence R, Houk K N, Jiménez-Osés Gonzalo, Sherman David H
Abstract excerpt
Macrolactonization of natural product analogs presents a significant challenge to both biosynthetic assembly and synthetic chemistry. In the preceding paper , we identified a thioesterase (TE) domain catalytic bottleneck processing unnatural substrates in the pikromycin (Pik) system, preventing the formation of epimerized macrolactones. Here, we perform molecular dynamics simulations showing the epimerized...
Topics
- Biocatalysis
- Catalytic Domain
- Cyclization
- Gain of Function Mutation
- Kinetics
- Macrolides
- Molecular Dynamics Simulation
- Mutation
- Polyketide Synthases
- Substrate Specificity