The Generation and Exploitation of Protein Mutability Landscapes for Enzyme Engineering

Jan-Ytzen van der Meer, Lieuwe Biewenga, Gerrit J Poelarends

Research output: Contribution to journalArticleAcademicpeer-review

31 Citations (Scopus)
225 Downloads (Pure)

Abstract

The increasing number of enzyme applications in chemical synthesis calls for new engineering methods to develop the biocatalysts of the future. An interesting concept in enzyme engineering is the generation of large-scale mutational data in order to chart protein mutability landscapes. These landscapes allow the important discrimination between beneficial mutations and those that are neutral or detrimental, thus providing detailed insight into sequence-function relationships. As such, mutability landscapes are a powerful tool with which to identify functional hotspots at any place in the amino acid sequence of an enzyme. These hotspots can be used as targets for combinatorial mutagenesis to yield superior enzymes with improved catalytic properties, stability, or even new enzymatic activities. The generation of mutability landscapes for multiple properties of one enzyme provides the exciting opportunity to select mutations that are beneficial either for one or for several of these properties. This review presents an overview of the recent advances in the construction of mutability landscapes and discusses their importance for enzyme engineering.

Original languageEnglish
Pages (from-to)1792-1799
Number of pages8
JournalChemBioChem
Volume17
Issue number19
DOIs
Publication statusPublished - 2016

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