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
