Engineering enzyme catalysis: an inverse approach.

Clare F Megarity

doi:10.1042/bsr20181107

Abstract

Enzymes’ inherent chirality confers their exquisite enantiomeric specificity and makes their use as green alternatives to chiral metal complexes or chiral organocatalysts invaluable to the fine chemical industry. The most prevalent way to alter enzyme activity in terms of regioselectivity and stereoselectivity for both industry and fundamental research is to engineer the enzyme. In a recent article by Keinänen et al., published in Bioscience Reports 2018, ‘Controlling the regioselectivity and stereoselectivity of FAD-dependent polyamine oxidases with the use of amine-attached guide molecules as conformational modulators’, an inverse approach was presented that focuses on the manipulation of the enzyme substrate rather than the enzyme. This approach not only uncovered dormant enantioselectivity in related enzymes but allowed for its control by the use of guide molecules simply added to the reaction solution or covalently linked to an achiral scaffold molecule.

Highlights

Flavo-enzymes that catalyse reactions involved in polyamine metabolism were investigated, namely human acetylpolyamine oxidase (APAO), human spermine oxidase (SMOX) and yeast polyamine oxidase (Fms1) [1]
Malfunction in polyamine metabolism is implicated in diseases such as cancer and diabetes [1]; it differs between bacteria, parasites and the host organism identifying it as a possible target pathway for novel drugs [2]
The research presented by Keinanen et al is valuable in terms of enzyme-catalysis for organic synthesis, and it informs at a fundamental level in terms of enzyme structure, catalytic mechanism and selectivity

Summary

Introduction

Flavo-enzymes that catalyse reactions involved in polyamine metabolism were investigated, namely human acetylpolyamine oxidase (APAO), human spermine oxidase (SMOX) and yeast polyamine oxidase (Fms1) [1]. The results from the in vivo study inspired the authors to initially investigate the activity of APAO with different substrate analogues that were chiral and the effect of aldehydes on the reaction.

Results

Conclusion