**Alexander Veljko Fejzagi´c 1, Jan Gebauer 2, Nikolai Huwa <sup>1</sup> and Thomas Classen 1,\***


Academic Editor: Josefina Aleu Received: 11 October 2019; Accepted: 31 October 2019; Published: 5 November 2019

**Abstract:** Halogens can be very important for active agents as vital parts of their binding mode, on the one hand, but are on the other hand instrumental in the synthesis of most active agents. However, the primary halogenating compound is molecular chlorine which has two major drawbacks, high energy consumption and hazardous handling. Nature bypassed molecular halogens and evolved at least six halogenating enzymes: Three kind of haloperoxidases, flavin-dependent halogenases as well as α-ketoglutarate and *S-*adenosylmethionine (SAM)-dependent halogenases. This review shows what is known today on these enzymes in terms of biocatalytic usage. The reader may understand this review as a plea for the usage of halogenating enzymes for fine chemical syntheses, but there are many steps to take until halogenating enzymes are reliable, flexible, and sustainable catalysts for halogenation.

**Keywords:** bromination; chlorination; pharmaceuticals; active agent synthesis; biocatalysis; haloperoxidase; halogenase
