Structural highlights
FunctionPublication Abstract from PubMedPlants contain rapidly evolving specialized enzymes that support the biosynthesis of functionally diverse natural products. In coumarin biosynthesis, a BAHD acyltransferase-family enzyme COSY was recently discovered to accelerate coumarin formation as the only known BAHD enzyme to catalyze an intramolecular acyl transfer reaction. Here we investigate the structural and mechanistic basis for COSY's coumarin synthase activity. Our structural analyses reveal an unconventional active-site configuration adapted to COSY's specialized activity. Through mutagenesis studies and deuterium exchange experiments, we identify a unique proton exchange mechanism at the alpha-carbon of the o-hydroxylated trans-hydroxycinnamoyl-CoA substrates during the catalytic cycle of COSY. Quantum mechanical cluster modeling and molecular dynamics further support this key mechanism for lowering the activation energy of the rate-limiting trans-to-cis isomerization step in coumarin production. This study unveils an unconventional catalytic mechanism mediated by a BAHD-family enzyme, and sheds light on COSY's evolutionary origin and its recruitment to coumarin biosynthesis in eudicots. Emergence of a proton exchange-based isomerization and lactonization mechanism in the plant coumarin synthase COSY.,Kim CY, Mitchell AJ, Kastner DW, Albright CE, Gutierrez MA, Glinkerman CM, Kulik HJ, Weng JK Nat Commun. 2023 Feb 3;14(1):597. doi: 10.1038/s41467-023-36299-1. PMID:36737607[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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