Tryptophan C5-, C6- and C7-Prenylating Enzymes Displaying a Preference for C-6 of the Indole Ring in the Presence of Unnatural Dimethylallyl Diphosphate Analogues


The behavior of four dimethylallyltryptophan synthases (DMATSs) (5-DMATS and 5-DMATSSc as tryptophan C5-prenyltransferases, and 6-DMATSSa and 6-DMATSSv as C6-prenyltransferases) and one l-tyrosine prenyltransferase with a tryptophan C7-prenyltransferase activity was investigated in the presence of two unnatural alkyl donors (methylallyl and 2-pentenyl diphosphate) and one benzyl donor (benzyl diphosphate). Detailed biochemical investigations revealed the acceptance of these dimethylallyl diphosphate (DMAPP) analogues by all tested enzymes with different relative activities. Enzyme products with the allyl or benzyl moiety attached to different positions were identified in the reaction mixtures, whereby C-6 alkylated or benzylated l-tryptophan was found as one of the main products. This observation demonstrates a preference of the five prenyltransferases toward C-6 of the indole ring in the presence of unnatural DMAPP derivatives. Molecular dynamics simulation experiments with a homologous model of 5-DMATS explained well its reactions with methylallyl and 2-pentenyl diphosphate. Furthermore this study expands significantly the potential usage of tryptophan prenylating enzymes as biocatalysts for Friedel–Crafts alkylation.


Julia Winkelblech, Mike Liebhold, Jakub Gunera, Xiulan Xie, Peter Kolb, Shu-Ming Li


Advanced Synthesis & Catalysis

Year, Volume, Page

2015, 357, 975



Tag Element Regiochemistry Product Substrate Cofactor Enzyme
PTDBREC00172 C Regular 6-DMATSSA
PTDBREC00173 C Regular 5-DMATS
PTDBREC00174 C Regular 6-DMATSSA
PTDBREC00175 C Regular 6-DMATSSV
PTDBREC00176 C Regular TyrPT
PTDBREC00177 C Regular 5-DMATSSC
PTDBREC00178 C Regular 5-DMATS
PTDBREC00179 C Regular TyrPT
PTDBREC00180 C Regular 5-DMATSSC
PTDBREC00181 C Reverse TyrPT
PTDBREC00182 C Regular TyrPT
PTDBREC00183 C Regular 6-DMATSSV
PTDBREC00184 C Regular 5-DMATSSC
PTDBREC00185 C Regular 6-DMATSSA
PTDBREC00186 C Regular 6-DMATSSV
PTDBREC00187 C Regular TyrPT
PTDBREC00188 C Regular 5-DMATSSC
PTDBREC00189 C Regular 5-DMATS
PTDBREC00190 C Regular TyrPT
PTDBREC00191 C Regular 5-DMATSSC
PTDBREC00192 C Regular TyrPT
PTDBREC00193 C Regular 5-DMATSSC
PTDBREC00194 C Regular TyrPT
PTDBREC00195 C Regular 5-DMATS
PTDBREC00196 C Regular 6-DMATSSA
PTDBREC00197 C Regular 6-DMATSSV
PTDBREC00198 C Regular 5-DMATS
PTDBREC00199 C Reverse 6-DMATSSA
PTDBREC00200 C Reverse 6-DMATSSV
PTDBREC00201 C Reverse 5-DMATSSC
PTDBREC00202 C Reverse 5-DMATS
PTDBREC00203 C Regular 6-DMATSSA
PTDBREC00204 C Regular 6-DMATSSV
PTDBREC00205 C Regular 5-DMATSSC
PTDBREC00206 C Regular TyrPT
PTDBREC00207 C Regular 6-DMATSSA
PTDBREC00208 C Regular 6-DMATSSV
PTDBREC00209 C Regular 5-DMATS
PTDBREC00210 C Reverse 6-DMATSSA
PTDBREC00211 C Reverse 6-DMATSSV
PTDBREC00212 C Reverse 5-DMATSSC
PTDBREC00213 C Reverse 5-DMATS
PTDBREC00214 C Regular 6-DMATSSA
PTDBREC00215 C Regular 6-DMATSSV
PTDBREC00216 C Regular 5-DMATS
PTDBREC00217 C Regular 5-DMATS
PTDBREC00218 C Regular 6-DMATSSA
PTDBREC00219 C Regular 6-DMATSSV
PTDBREC00220 C Regular TyrPT
PTDBREC00221 C Regular 5-DMATSSC
PTDBREC00222 C Reverse TyrPT
PTDBREC00223 C Regular 5-DMATSSC