Malbrancheamide is a fungal natural product with significant vasorelaxation effects and potential as a cardiovascular therapeutic. The dichlorination of the indole ring is key for its biological activity, and this transformation is performed by the flavin dependent halogenase MalA. This enzyme utilizes a proposed chloramine lysine intermediate to iteratively and selectively chlorinate its natural substrate premalbrancheamide. Halogenases can provide orthogonal selectivity to many chemical methods, making them useful for pharmaceutical applications, while providing selective methods for late-stage functionalization. This investigation focuses on the substrate scope of the halogenase on complex pharmaceutically relevant substrates in collaboration with the Novartis Institutes for Biomedical Research. The bromination and chlorination reaction conditions were optimized, and the products were structurally characterized by NMR spectroscopy to gain further understanding of the versatility of the wild type enzyme and its mutants
