The hydroxylation of fatty acids is an appealing reaction in synthetic chemistry, although the lack of selective catalysts hampers its industrial implementation. In this study, we have engineered a highly regioselective fungal peroxygenase for the ω-1 hydroxylation of fatty acids with quenched stepwise over-oxidation. One single mutation near the Phe catalytic tripod narrowed the heme cavity, promoting a dramatic shift toward subterminal hydroxylation with a drop in the over-oxidation activity. While crystallographic soaking experiments and molecular dynamic simulations shed light on this unique oxidation pattern, the selective biocatalyst was produced by Pichia pastoris at 0.4 g L⁻¹ in a fed-batch bioreactor and used in the preparative synthesis of 1.4 g of (ω-1)-hydroxytetradecanoic acid with 95 % regioselectivity and 83 % ee for the S enantiomer.

The chemoenzymatic oxidative decarboxylation of glutamic acid to the corresponding nitrile using the vanadium chloroperoxidase from Curvularia inaequalis (CiVCPO) as HOBr generation catalysts has been investigated. Product inhibition was identified as major limitation. Nevertheless, 1630000 turnovers and k_cat of 75 s⁻¹ were achieved using 100 mM glutamate. The semi-preparative enzymatic oxidative decarboxylation of glutamate was also demonstrated.

The scale-up of chemoenzymatic bromolactonization to 100 g scale is presented, together with an identification of current limitations. The preparative-scale reaction also allowed for meaningful mass balances identifying current bottlenecks of the chemoenzymatic reaction.

Haloperoxidases are very active catalysts for the in situ generation of electrophilic halide species for oxidative halogenation reactions. In the synthetic community, these catalysts, however, are not widely used. The aim of this mini-review is to critically summarise the current state-of-the-art of haloperoxidase catalysis for organic synthesis. We hope that the excellent catalytic performance of these catalysts will trigger more chemists to consider them in their synthesis planning.