Recent Advances in Synthetic Application and Engineering of Halogenases

Abstract

Hannah Minges received her B.Sc. and M.Sc. degrees in biochemistry from Bielefeld University and specialized in biocatalysis. From 2016-2020 she worked in the research group Organic and Bioorganic Chemistry at Bielefeld University where she obtained her PhD degree in 2020 under supervision of Prof. Dr. Norbert Sewald. She is particularly interested in enzyme engineering and optimization of biocatalysts by applying random and rational evolution to facilitate the application of enzymes in organic synthesis. Norbert Sewald studied chemistry at the Technical University of Munich. Having obtained his PhD degree in organic chemistry, he worked in the group of Prof. J. E. Baldwin

Novel Arylindigoids by Late‐Stage Derivatization of Biocatalytically Synthesized Dibromoindigo

“…Assembly of the indigoid scaffold is achieved by stepwise C−H functionalization utilizing selective halogenation and hydroxylation starting from l ‐tryptophan ( 3 , Scheme 1 B). [15] Various recent achievements underscore that flavin‐dependent tryptophan halogenases are capable of regioselective aryl halogenation using O 2 , FADH 2 and a halide salt [33, 34] . Current efforts on random and targeted engineering, immobilization and combination with chemocatalysis considerably extended the synthetic utility of these enzymes [35–40] .…”

“…[15] Various recent achievements underscore that flavin-dependent tryptophan halogenases are capable of regioselective aryl halogenation using O 2 ,F ADH 2 and ah alide salt. [33,34] Currente fforts on random and targeted engineering, immobilization and combination with chemocatalysis considerably extended the synthetic utility of thesee nzymes. [35][36][37][38][39][40] Recent reportsa lso showcase applicationsofhalogenases for the synthesis of valuablechemicals using cascades in vivo and in vitro.…”

Enzymatic Late‐Stage Modifications: Better Late Than Never

“…To obtain an overview of the advancements in halogenating enzymes, Minges and Sewald published a recent update on state‐of‐the‐art applications of halogenases. [103] In addition, more details on biocatalytic halogenation are summarised in Supporting Section 4 (see Supporting Information).…”

Enzymkatalysierte späte Modifizierungen: Besser spät als nie

“…Oxidative Halogenasen bilden entweder formal eine “X + ”‐Spezies (X=Cl, Br, I) oder ein Halogenradikal, wohingegen Fluorinasen ein nucleophiles Fluorid‐Ion übertragen (Schema 11). Für einen Überblick über die Fortschritte und aktuelle Anwendungen der halogenierenden Enzyme verweisen wir auf einen aktuellen Aufsatz von Minges und Sewald [103] . In Ergänzung dazu sind weitere Details über die biokatalytische Halogenierung in Supporting Section 4 zusammengefasst (siehe Hintergrundinformationen).…”