Halogenases: a palette of emerging opportunities for synthetic biology–synthetic chemistry and C–H functionalisation

Charlotte Crowe, Samuel Molyneux, Sunil Sharma, Ying Zhang, Danai Gkotsi, Helen Connaris, Rebecca Goss (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

54 Citations (Scopus)
110 Downloads (Pure)


The enzymatic generation of carbon–halogen bonds is a powerful strategy used by both nature and synthetic chemists to tune the bioactivity, bioavailability and reactivity of compounds, opening up the opportunity for selective C–H functionalisation. Genes encoding halogenase enzymes have recently been shown to transcend all kingdoms of life. These enzymes install halogen atoms into aromatic and less activated aliphatic substrates, achieving selectivities that are often challenging to accomplish using synthetic methodologies. Significant advances in both halogenase discovery and engineering have provided a toolbox of enzymes, enabling the ready use of these catalysts in biotransformations, synthetic biology, and in combination with chemical catalysis to enable late stage C–H functionalisation. With a focus on substrate scope, this review outlines the mechanisms employed by the major classes of halogenases, while in parallel, it highlights key advances in the utilisation of the combination of enzymatic halogenation and chemical catalysis for C–H activation and diversification.
Original languageEnglish
Pages (from-to)9443-9481
Number of pages40
JournalChemical Society Reviews
Issue number17
Early online date9 Aug 2021
Publication statusPublished - 7 Sept 2021


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