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Updated: Oct 15, 2025

Biosynthesis of a Flavonol from a Flavanone by Establishing a One-pot Bienzymatic Cascade
Published on: August 14, 2019
A Promiscuous Halogenase for the Derivatization of Flavonoids
Dominik Kolling1, Marc Stierhof1, Constanze Lasch1
1Department of Pharmaceutical Biotechnology, Saarland University, 66123 Saarbruecken, Germany.
Abstract:
Halogenation often improves the bioactive properties of natural products and is used in pharmaceutical research for the generation of new potential drug leads. High regio- and stereospecificity, simple reaction conditions and straightforward downstream processing are the main advantages of halogenation using enzymatic biocatalysts compared to chemical synthetic approaches. The identification of new promiscuous halogenases for the modification of various natural products is of great interest in modern drug discovery. In this paper, we report the identification of a new promiscuous FAD-dependent halogenase, DklH, from Frankia alni ACN14a. The identified halogenase readily modifies various flavonoid compounds, including those with well-studied biological activities. This halogenase has been demonstrated to modify not only flavones and isoflavones, but also flavonols, flavanones and flavanonols. The structural requirements for DklH substrate recognition were determined using a feeding approach. The homology model of DklH and the mechanism of substrate recognition are also proposed in this paper.
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