Fatty acids derived from renewable resources, such as vegetable oils, serve as essential feedstocks in various industries, including surfactants, cosmetics, lubricants, and polymers. Although current industrial applications of fatty acids are mainly centered around carboxylate group transformations, recent advancements in biocatalysis have opened new possibilities for converting fatty acids into valuable chemical building blocks. This contribution critically assesses novel biocatalytic transformations of fatty acids, including hydroxylation of the alkyl chain, epoxidation of C═C double bonds, reduction of the carboxylate group, and decarboxylation. These reactions hold great potential for producing important intermediates for chemical synthesis.

Practical Application: The enzymatic valorization of fatty acids offers transformative potential for sustainable oleochemical synthesis, presenting practical applications across various industries. Hydroxylated and epoxidized fatty acids are promising precursors for the production of polyesters, bio-based lubricants, and surfactants. Sophorolipids, derived from hydroxylated fatty acids, are gaining attraction as renewable biosurfactants with applications in detergents and cosmetics. Epoxidized fatty acids serve as intermediates for eco-friendly adhesives, coatings, and polymers. Furthermore, decarboxylation reactions yield alkanes, viable as biofuels, whereas reductions of carboxyl groups enable selective synthesis of aldehydes and alcohols for fragrances and pharmaceutical intermediates. The scalability of these biocatalytic transformations, combined with their mild operational conditions and high specificity, can substantially reduce environmental impact and production costs. These applications highlight biocatalysis as a pivotal technology for advancing the chemical industry toward sustainable practices.

Heme-containing unspecific peroxygenases (UPOs) have attracted significant attention as biocatalysts for oxidation reactions due to their ability to function without expensive nicotinamide cofactors. In the recent study, the UPO from aspergillus brasiliensis (AbrUPO) is found to catalyze the aromatic hydroxylation of substituted benzenes, a feature that distinguishes AbrUPO from other reported wild-type UPOs. To elucidate the underlying factors in the active site and substrate access channel of AbrUPO—which contains fewer phenylalanine residues compared to other UPOs that primarily catalyze benzylic hydroxylation—twenty two AbrUPO variants with single, double, triple, or quadruple amino acid substitutions were constructed to mimic the active sites or substrate access channels of other UPOs. A number of mutated variants exhibited altered activity and selectivity, and several positions were identified that influence enzyme chemoselectivity. Among them, substitution of alanine at position 186 with bulkier residues such as phenylalanine or leucine lead to a shift in chemoselectivity toward alkyl chain hydroxylation of substituted benzenes. Molecular docking studies indicated that the A186F mutation restricts the flexibility and reorientation of ethylbenzene in the active site of AbrUPO, thereby preventing oxidation at the aromatic ring while promoting benzylic hydroxylation.

Peroxygenases represent a class of versatile heme-thiolate enzymes capable of catalysing highly selective oxyfunctionalisation reactions, particularly the hydroxylation of non-activated C-H bonds. This transformation, which poses substantial challenges in conventional organic synthesis, underscores the potential of peroxygenases in green chemistry applications. While cytochrome P450 monooxygenases have long been the primary focus for such biocatalytic transformations, their industrial adoption has been limited due to complex electron transfer chains and cofactor requirements. In contrast, peroxygenases bypass these limitations by directly utilising hydrogen peroxide (H2O2) to activate the catalytic heme site, thereby circumventing the oxygen dilemma typically encountered in P450 catalysis. Key milestones in peroxygenase research include the identification of chloroperoxidase from Caldariomyces fumago and the subsequent discovery of unspecific peroxygenases, such as those from Agrocybe aegerita, which exhibit broad substrate specificity and high catalytic efficiency. Here, we explore the mechanistic pathway of peroxygenase-catalysed reactions, emphasising the formation and decay of Compound I and the catalytic cycle’s various functional outcomes. Critical aspects such as in situ H2O2 generation to mitigate enzyme inactivation, substrate loading strategies for practical applications, and the role of enzyme and reaction engineering in enhancing regio- and stereoselectivity are examined. Additionally, we address challenges in reaction scalability and operational stability for preparative-scale applications, offering insights into innovative protocols involving immobilised enzymes and non-aqueous reaction media. This review highlights recent advancements in the peroxygenase field and underscores the enzyme’s promising role in sustainable oxyfunctionalisation reactions.