Scientists from Manchester have developed a template to predict if amines can be deracemised by a specific enzyme. 

Chirality is extremely important for chemicals with bio-applications and a group led by Professor Nicholas Turner at the University of Manchester have used directed evolution to make enzymes (variants of monoamine oxidase (MAO-N)) that can be used to produce chiral amines from racemic mixtures. To encourage the use of the enzyme as a biocatalyst, the team have created a template for substrate design and selection. 

By superimposing all the substrates that are known to be active, the group created a hypothetical amine that satisfies the steric demands of the enzyme. To prove the effectiveness of the template, a suitable target (crispine A) was found that satisfied the constraints of the model and could be used to demonstrate that the template works. 

Crispine A is a natural product from Carduus crispus that has been shown to be cytotoxic to certain cancer cells, while a less functionalised analogue has been shown to exhibit antidepressant-like activity. Racemic mixtures of both compounds were synthesised before being subjected to a reducing agent and Escherichia coli  cells expressing a variant of MAO-N. After the reaction, both compounds were found to exist as the (R)-isomer in 97% e.e., demonstrating the effectiveness of the template in identifying racemic amine substrates that can be subjected to deracimisation by MAO-N. 

'It is hoped that this model will encourage the use of this new catalyst and bring its attention to a wider audience,' says Nicholas Turner. 'This new approach will save time and aid in the planning of synthetic routes to chiral amines.'

Laura Howes