From Commercial Enzymes to Biocatalysts Designed by Protein Engineering

This account provides a personal view on the development of biocatalysis over the last two decades. Examples include the use of commercial enzymes, such as lipases, (recombinant) esterases, transaminases, and Baeyer-Villiger monooxygenases for the synthesis of optically pure compounds. The opportunity provided by modern protein engineering methods to tailor design an enzyme for a given scientific problem (substrate scope, selectivity, stability) is emphasized together with concepts to boost this technology in terms of timelines and success. 1 Introduction 2 Unexpected Discoveries 2.1 To Protect and Serve 2.2 'Abnormal' Access to beta-Amino Acids 3 Defined Enzyme Is Better Than Crude Extract 4 New Horizons Opened by Protein Engineering 4.1 Random Mutagenesis Can Give Random Results 5 Exploring Sequence and Structure Databases 5.1 Massive Alignment Identifies Evolutionary Variations 5.2 Fixing Wrong Annotations Can Yield a Toolbox of Novel Enzymes 6 Conclusion