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Targeted enzyme discovery using metal-coordination mining | Nature
The recent revolution in genome sequencing and protein structure prediction has opened new frontiers in understanding, predicting and designing enzyme function1,2. Central to these efforts is the discovery and functional annotation of novel enzymes, which is essential for elucidating the connection between genotype and phenotype and for developing biocatalysts for industrial applications. However, accurately predicting enzymatic function remains a major challenge, and the discovery of new enzymes often relies on serendipity. Here we present a metal-coordination-guided strategy that uses atomic-level mechanistic principles to mine protein structure databases for the targeted discovery of metalloenzymes. We apply this framework to the AlphaFold2 Protein Structure Database to identify new members of the FeII/α-ketoglutarate-dependent halogenase family, which selectively functionalize unactivated C(sp3)-H-bonds, a crucial transformation in the production of pharmaceuticals and other high-v
