Specific Enzymatic Halogenation-From the Discovery of Halogenated Enzymes to Their Applications In Vitro and In Vivo

• Published in: Angewandte Chemie (International ed.) Vol. 55; no. 22; pp. 6374 - 6389
• Main Authors: Weichold, Veit, Milbredt, Daniela, van Pée, Karl-Heinz
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 23.05.2016
• Subjects: Biocatalysis; biosynthesis; enzyme catalysis; halogenases; Halogenation; haloperoxidases; Molecular Structure; Oxidoreductases - chemistry; Oxidoreductases - metabolism; Substrate Specificity; halogenases; haloperoxidases; enzyme catalysis; halogenation; biosynthesis
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201509573

During the last 20 years, focus has shifted from haloperoxidases to flavin‐dependent and non‐heme‐iron halogenases because of their proven involvement in the biosynthesis of halogenated metabolites in different organisms and the regioselectivity of their reactions. During the first 10–12 years, the main research topics were the detection of halogenases as well as the elucidation of three‐dimensional structures and reaction mechanisms. This Review mainly deals with studies on halogenating enzymes published between 2010 and 2015. It focusses on the elucidation of the involvement of halogenating enzymes in halometabolite biosynthesis, application of halogenases in in vivo and in vitro systems, in vivo modification of biosynthetic pathways in bacteria and plants, improvement of enzyme stability, broadening of substrate specificity, and the combination of biocatalysis with chemical synthesis to produce new compounds. Coming of age: The understanding of biological halogenation has increased enormously in the last 20 years. While the first 10 years were mostly dedicated to the detection of halogenating enzymes, in the last 10 years the connection of the enzymes with biosynthetic pathways by showing in vitro activity, investigating substrate specificities, as well as applications and improvement of the enzymes came into focus.