Substrate promiscuity of secondary metabolite enzymes: prenylation of hydroxynaphthalenes by fungal indole prenyltransferases |
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Authors: | Xia Yu Xiulan Xie Shu-Ming Li |
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Institution: | 1.Institut für Pharmazeutische Biologie und Biotechnologie,Philipps-Universit?t Marburg,Marburg,Germany;2.Zentrum für Synthetische Mikrobiologie,Philipps-Universit?t Marburg,Marburg,Germany;3.Fachbereich Chemie,Philipps-Universit?t Marburg,Marburg,Germany |
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Abstract: | 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. |
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