Abstract
Prenyltransferases of the dimethylallyltryptophan synthase (DMATS) superfamily are involved in the biosynthesis of secondary metabolites and contribute as modification enzymes significantly to structural diversity of natural products. They show usually broad specificity toward their aromatic substrates with regiospecific prenylations on aromatic rings. However, most members of this superfamily exhibit a high specificity toward their prenyl donors and usually accept exclusively dimethylallyl diphosphate (DMAPP). Recently, several indole prenyltransferases from this family were also demonstrated to accept unnatural DMAPP analogs such as methylallyl, 2-pentenyl and benzyl diphosphate for alkylation, or benzylation of the indole ring. Partial or complete shift of the substitution position was observed for these enzymes. In this study, we report the acceptance of these DMAPP analogs by two tyrosine O-prenyltransferases TyrPT from Aspergillus niger and SirD from Leptosphaeria maculans for alkylation or benzylation of tyrosine and derivatives. NMR and mass spectrometry (MS) analyses of nine isolated enzyme products confirmed the regiospecific O- or N-alkylation or benzylation at position C-4 of the aromatic ring, which is the same prenylation position of these enzymes in the presence of DMAPP.
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Acknowledgments
We thank Nina Zitzer and Stefan Newel for taking MS and NMR spectra, respectively. This work was supported in part by grants from the Deutsche Forschungsgemeinschaft (Li844/4-1 to S.-M L.). Huili Yu is a recipient of a scholarship from the China Scholarship Council.
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Yu, H., Liebhold, M., Xie, X. et al. Tyrosine O-prenyltransferases TyrPT and SirD displaying similar behavior toward unnatural alkyl or benzyl diphosphate as their natural prenyl donor dimethylallyl diphosphate. Appl Microbiol Biotechnol 99, 7115–7124 (2015). https://doi.org/10.1007/s00253-015-6452-1
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DOI: https://doi.org/10.1007/s00253-015-6452-1