Strategies for Altering Enzyme Reaction Specificity for Applied Biocatalysis

Author(s): Per Berglund , Seongsoon Park .

Journal Name: Current Organic Chemistry

Volume 9 , Issue 4 , 2005

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Abstract:

The fact that many enzymes have broad substrate specificity has been a property of fundamental importance for the widespread applications of enzymes in synthetic chemistry. Many enzymes can, in addition, catalyze completely different reactions compared to their natural ones. The possibility of using molecular biology techniques to control such catalytic plasticity of enzymes in order to establish completely new reaction specificity in the active site is the topic for this review. The examples are subdivided according to six different approaches used (i - vi) for engineering of the reaction specificity. The first approach (i) is the random method of directed evolution to achieve new reaction specificity. Other approaches involve strategies where the reaction specificity of a known enzyme is implemented into another, closely related, enzyme by substituting key amino acid residues selected either by (ii) sequence or (iii) structural overlap of the two enzymes. Yet other approaches involve substitution of key amino acid residues to introduce new reaction specificity without comparing with a template enzyme (iv) and the introduction of a complete catalytic machinery (v). The final approach is the introduction of an active site into a non-catalytic protein (vi). These six different approaches for altering the reaction chemistry of enzymes each represent a powerful tool for controlling the catalytic plasticity of enzymes. The prospect for these altered enzymes as catalysts in synthetic chemistry is very large although examples of practical use are rare and still challenging. The progress in the area of altering enzyme reaction specificity will result in a continued development towards the goal of creating tailor-made enzymes for synthetic chemistry.

Keywords: stereoselectivity, natural substrate, catalytic plasticity, dna shuffling

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Article Details

VOLUME: 9
ISSUE: 4
Year: 2005
Page: [325 - 336]
Pages: 12
DOI: 10.2174/1385272053174967
Price: $58

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