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.

A tyrosinase‐mediated arylation towards a variety of different building blocks is presented. Utilizing phenol or simple substituted phenols, the corresponding quinones are synthesized in a two‐step procedure by an enzyme‐catalyzed oxidation (tyrosinase from Aspergillus oryzae). The activated intermediates undergo a 1,4‐addition with selected β‐dicarbonyl compounds. Starting from phenol, yields of isolated product for the hydroxylation‐oxidation‐arylation sequence range from 43–77 %, whereas substituted acceptors provided 9–55 %, only. Different substitution patterns on phenol revealed that electron donating functionalities are preferentially accepted to electron withdrawing ones, whereas ortho‐substituted phenols are not accepted at all.

Introduction: The antimicrobial pyrrolnitrin from Pseudomonas strains is formed in four steps from tryptophan and comprises two flavin-dependent halogenases. Both PrnC and PrnA can carry out regioselective chlorination and bromination and are carrier protein-independent. Whilst the tryptophan halogenase PrnA has been studied in detail in the past, this study focuses on the pyrrole halogenating enzyme PrnC.Methods: The halogenating enzyme PrnC, as well as the essential electron suppliers, the flavin reductases, have been produced soluble in E. coli. Furthermore, a screening of a rational compound library revealed that the pyrrole is essential for substrate recognition; however, the substitution pattern of the benzene ring is not limiting the catalysis.Results and discussion: This renders PrnC to be a synthetically valuable enzyme for the synthesis of pyrrolnitrin congeners. For its natural substrate monodechloroaminopyrrolnitrin (MDA), the KM value was determined as 14.4 ± 1.2 µM and a kcat of 1.66 ± 0.02 min−1, which is comparable to other halogenases.