Novel Asymmetric Functionalizations of Alkenes by Modular Cascade Biocatalysis
Catalytic asymmetric transformation is of great importance in the preparation of chiral chemicals for the manufacturing of pharmaceuticals, agrochemicals, and specialty chemicals. Here, we develop three novel types of regio- and enantioselective multiple oxy- and amino-functionalizations of terminal alkenes via cascade biocatalysis to produce chiral α-hydroxy acids, 1,2-amino alcohols, and α-amino acids, respectively. Basic enzyme modules 1-4 are developed to convert alkenes to (S)-1,2-diols, (S)-1,2-diols to (S)-α-hydroxy acids, (S)-1,2-diols to (S)-amino alcohols, and (S)-α-hydroxy acids to (S)-α-amino acids, respectively. Engineering of enzyme modules 1 & 2, 1 & 3, and 1, 2, & 4 in Escherichia coli affords three biocatalysts containing 4-8 enzymes for one-pot conversion of 11 different styrenes to the corresponding 11 (S)-α-hydroxy acids, 11 (S)-amino alcohols, and 11 (S)-α-amino acids in high ee and high yields, respectively. The new types of asymmetric alkene functionalizations provide green, safe, and useful alternatives to the chemical syntheses of these compounds. The modular approach for engineering multistep cascade biocatalysis is useful for developing other new types of one-pot biotransformations for chemical synthesis.
This work was published in Nature Communications on Jun 14, 2016 (DOI: 10.1038/ncomms11917).
Corresponding author(s) Webpage: http://cheed.nus.edu.sg/stf/chelz/index.html