Intramolecular Stereoselective Stetter Reaction Catalyzed by Benzaldehyde Lyase

Abstract

The reliable design and prediction of enzyme promiscuity to access transformations not observed in nature remains a long‐standing challenge. Herein, we present the first example of an intramolecular stereoselective Stetter reaction catalyzed by benzaldehyde lyase, guided by the rational structure screening of various ThDP‐dependent enzymes using molecular dynamics (MD) simulations. After optimization, high productivity (up to 99 %) and stereoselectivity (up to 99:1 e.r.) for this novel enzyme function was achieved.

Biocatalysis making waves in organic chemistry

“…Elegant analysis of these binding pockets allowed the engineering thereof. [68][69][70][71][72] As a result excellent control of the donor and acceptor molecule as well as the stereoselectivity was gained (Scheme 6). This work was further extended by engineering a decarboxylase in such a way that it could admit formaldehyde as acceptor, making it one of the few enzymes that can convert this toxic compound and at the same time enabling C1 chemistry also for the ThDPdependent enzymes.…”

Enzymatic strategies for asymmetric synthesis

“… 224,225 An intramolecular nondecarboxylative version was developed with a benzaldehyde lyase and allowed the generation of chiral chroman-4-one derivatives with up to 98% ee. 226 …”

Modeling‐Assisted Design of Thermostable Benzaldehyde Lyases from Rhodococcus erythropolis for Continuous Production of α‐Hydroxy Ketones

“…The BAL from Pseudomonas fluorescens [4,5] ( Pf BAL) is the only experimentally confirmed representative in this enzyme class recorded in the BRENDA [6] and TEED [7] database to date (for more detailed analysis of TEED database see supporting information page 20). It has an broad substrate spectrum [8,9] and can also catalyze C−N bond formations, [10] cyclizations [11] and intramolecular Stetter reactions [12] . Moreover, via rational engineering of its binding site, Pf BAL was successfully altered to perform benzoylformate decarboxylase [13] or formolase reactions [14] .…”