Journal
ACS CATALYSIS
Volume 10, Issue 22, Pages 13630-13640Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acscatal.0c03758
Keywords
biocatalysis; Pictet-Spengler reaction; strictosidine synthase; enantioselectivity; reaction mechanism; computational chemistry
Categories
Funding
- Swedish Research Council (VR)
Ask authors/readers for more resources
Strictosidine synthase (STR) catalyzes the Pictet-Spengler (PS) condensation between tryptamine and secologanin, leading to the formation of (S)-strictosidine. The product is a central intermediate in the biosynthesis of various indole alkaloids, many of which are pharmaceutically important. STRs have relatively broad scopes for both the amine and aldehyde substrates, making them attractive biocatalyst candidates for applications in organic synthesis. An interesting feature of STR discovered recently is the switched enantiopreference of the reaction using short-chain aliphatic aldehydes in comparison to the natural secologanin substrate. Herein, we use quantum chemical calculations to investigate the detailed reaction mechanism and the origins of enantioselectivity of STR, considering both natural and non-natural substrates. The calculated overall barrier is in a good agreement with the measured rate constant, and the nature of the rate-determining step is consistent with kinetic isotope effect experiments. Importantly, the enantioselectivity for the reactions of both natural and non-natural substrates are well reproduced. A systematic analysis of energy profiles of the entire reactions and the geometries of the key transition states and intermediates along the pathways leading to the different enantiomers of the products provides a rationalization for the observed inversion of enantioselectivity.
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