Catalytic mechanism underlying the regiospecificity of coumarin-substrate transmembrane prenyltransferases in Apiaceae

Plant Cell Physiol. 2024 Nov 22:pcae134. doi: 10.1093/pcp/pcae134. Online ahead of print.

Abstract

Plant membrane-bound prenyltransferases (PTs) catalyse the transfer of prenyl groups to acceptor substrates, phenols, using prenyl diphosphates as the donor substrate. The presence of prenyl residues in the reaction products, prenylated phenols, is key to the expression of a variety of physiological activities. Plant PTs generally exhibit high specificities for both substrate recognition and prenylation sites, while the molecular mechanism involved in these enzymatic properties is largely unknown. In this study, we performed a systematic biochemical analysis to elucidate the catalytic mechanism responsible for the reaction specificity of plant PTs. Using two representative PTs, PsPT1 and PsPT2, from parsnip (Pastinaca sativa, Apiaceae), which differ only in the regiospecificity of the prenylation site, we performed domain swapping and site-directed mutagenesis of these PTs, followed by detailed enzymatic analysis combined with three-dimensional modelling. As a result, we discovered the domains that control prenylation site specificity and further defined key amino acid residues responsible for the catalytic mechanism. In addition, we showed that the control mechanism of prenylation specificity revealed here is also highly conserved among coumarin-substrate PTs. These data suggest that the regulatory domain revealed here is commonly involved in prenylation regiospecificity in Apiaceae PTs.

Keywords: Pastinaca sativa; Apiaceae; UbiA superfamily; coumarin; membrane-bound prenyltransferase; regiospecificity.