Substrate promiscuity of secondary metabolite enzymes: prenylation of hydroxynaphthalenes by fungal indole prenyltransferases


Fungal prenyltransferases of the dimethylallyltryptophan synthase (DMATS) superfamily share no sequence, but structure similarity with the prenyltransferases of the CloQ/NphB group. The members of the DMATS superfamily have been reported to catalyze different prenylations of diverse indole or tyrosine derivatives, while some members of the CloQ/NphB group used hydroxynaphthalenes as prenylation substrates. In this study, we report for the first time the prenylation of hydroxynaphthalenes by the members of the DMATS superfamily. Three tryptophan-containing cyclic dipeptide prenyltransferases (AnaPT, CdpNPT and CdpC3PT), one tryptophan C7-prenyltransferase and one tyrosine O-prenyltransferase (SirD) were incubated with naphthalene and 11 derivatives. The enzyme activity and preference of the tested prenyltransferases towards hydroxynaphthalenes differed clearly from each other. For an accepted substrate, however, different enzymes produced usually the same major prenylation product, i.e. with a regular C-prenyl moiety at para- or ortho-position to a hydroxyl group. Regularly, O-prenylated and diprenylated derivatives were also identified as enzyme products of substrates with low conversion rates and regioselectivity. This was unequivocally proven by mass spectrometry and nuclear magnetic resonance analyses. The K (M) values and turnover numbers (k (cat)) of the enzymes towards selected hydroxynaphthalenes were determined to be in the range of 0.064-2.8 mM and 0.038-1.30 s(-1), respectively. These data are comparable to those obtained using indole derivatives. The results presented in this study expanded the potential usage of the members of the DMATS superfamily for production of prenylated derivatives including hydroxynaphthalenes.


Xia Yu, Xiulan Xie, Shu-Ming Li


Applied Microbiology and Biotechnology

Year, Volume, Page

2011, 92, 737



Tag Element Regiochemistry Product Substrate Cofactor Enzyme
PTDBREC00443 C Regular AnaPT
PTDBREC00444 C Regular 7-DMATS
PTDBREC00445 C Regular CdpNPT
PTDBREC00446 C Regular CdpNPT
PTDBREC00447 C Regular AnaPT
PTDBREC00448 C Regular AnaPT
PTDBREC00449 C Regular 7-DMATS
PTDBREC00450 C Regular 7-DMATS
PTDBREC00451 C Regular CdpNPT
PTDBREC00452 C Regular CdpNPT
PTDBREC00453 C Regular CdpC3PT
PTDBREC00454 C Regular AnaPT
PTDBREC00455 C Regular CdpC3PT
PTDBREC00456 C Regular AnaPT
PTDBREC00457 C Regular AnaPT
PTDBREC00458 C Regular AnaPT
PTDBREC00459 C Regular AnaPT
PTDBREC00460 O Regular AnaPT
PTDBREC00461 C Regular AnaPT
PTDBREC00462 C Regular AnaPT
PTDBREC00463 C Regular AnaPT
PTDBREC00464 C Regular AnaPT
PTDBREC00465 C Regular 7-DMATS
PTDBREC00466 C Regular 7-DMATS
PTDBREC00467 C Regular CdpNPT
PTDBREC00468 C Regular AnaPT
PTDBREC00469 O Regular AnaPT
PTDBREC00470 C Regular AnaPT
PTDBREC00471 C Regular AnaPT
PTDBREC00472 C Regular AnaPT
PTDBREC00473 C Regular AnaPT
PTDBREC00474 C Regular AnaPT
PTDBREC00475 C Regular 7-DMATS
PTDBREC00476 C Regular 7-DMATS
PTDBREC00477 O Regular 7-DMATS
PTDBREC00478 C Regular 7-DMATS
PTDBREC00479 C Regular 7-DMATS
PTDBREC00480 C Regular CdpNPT
PTDBREC00481 O Regular CdpNPT
PTDBREC00482 C Regular CdpNPT
PTDBREC00483 C Regular CdpNPT
PTDBREC00484 C Regular CdpC3PT
PTDBREC00485 C Regular CdpC3PT
PTDBREC00486 C Regular 7-DMATS