Enzymatic halogenation of flavonoids by a fungal flavin-dependent halogenase


Fidan Ö.

III. International Enzyme and Bioprocess Days, Tokat, Turkey, 9 - 11 September 2022, pp.1

  • Publication Type: Conference Paper / Summary Text
  • City: Tokat
  • Country: Turkey
  • Page Numbers: pp.1
  • Abdullah Gül University Affiliated: Yes

Abstract

Flavonoids are important natural products with various biological activities such as anticancer, antiviral, antioxidant, anti-inflammatory and antimicrobial effects. Similarly, halogenated molecules occupy a significant portion of drugs on the market or in the development pipeline for pharmaceutical industry. Nevertheless, halogenated natural products are quite rare in nature. Currently, chemical halogenation is the common approach for the generation of halogenated drug molecules, which exhibit improved biological activities and enhanced pharmacokinetic properties. For instance, compared to chrysin and other tested flavonoids, halogenated chrysins have indicated stronger antiviral activity against dengue and Zika viruses. While chemical halogenation is limited by its poor selectivity and harsh reaction conditions, enzymatic halogenation represents a green and effective method to prepare halogenated compounds. In this study, we conducted the biotransformation of various flavonoids in engineered Escherichia coli BL21(DE3) expressing fungal flavin-dependent halogenase (Rdc2). We successfully halogenated chrysin, quercetin, naringenin, apigenin and hesperetin to yield a series of halogenated flavonoids. The halogenated flavonoids were purified and characterized with LC-MS and NMR. This work not only offers a green method for the halogenation of natural products, particularly flavonoids, but also expands the chemical repertoire of natural products by generating novel halogenated compounds.