Recent trends in the identification and engineering of halogenases

Abstract

Halogenation significantly enhances the biological activity, stability, and solubility of organic molecules, and thus is a crucial modification in the biotechnology and pharmaceutical industries. Halogenases, the core enzymes responsible for this transformation, are invaluable tools for the selective incorporation of halogens into diverse substrates, offering vast potential in drug development and synthetic biology. Recent discoveries of novel classes of halogenases have substantially expanded the repertoire of enzymatic halogenation. In parallel, remarkable progress in the protein engineering of halogenases is leading to unprecedented opportunities in the synthesis of novel compounds. These efforts have not only expanded the substrate scope, improved the selectivity, and enhanced the catalytic activity but also demonstrated their capacity for new-to-nature reactions. This perspective article highlights critical developments in the identification and engineering of halogenases, underscoring their growing significance in biocatalysis and sustainable chemical production. Continued exploration of novel halogenases, coupled with advanced protein engineering strategies, will open new frontiers in biocatalyst development and drug discovery.