S80: Prenyl transfer to aromatic substrates: Friedel-Crafts reactions in the biosynthesis of secondary metabolites in microorganisms

Aromatic prenyltransferases catalyze the transfer of prenyl moieties to aromatic acceptor molecules and give rise to an astounding diversity of primary and secondary metabolites in plants, fungi and bacteria. Recently, a new family of prenyltransferases has been discovered in bacteria of the genus Streptomyces. The members of this family are characterised by a new protein fold, termed PT barrel, consisting of five repetitive ααββ elements, with the antiparallel β strands forming a central barrel. These enzymes catalyze Friedel-Crafts alkylations of aromatic substrates, i.e. the formation of carbon-carbon-bonds between C-1 or C-3 of the isoprenoid substrate and an aromatic carbon of the acceptor substrate. In contrast to the membrane-bound aromatic prenyltransferases of ubiquinone, menaquinone and plastoquinone biosynthesis, the enzymes containing the PT barrel are soluble proteins and do not contain (N/D)DxxD motifs for binding of the isoprenoid substrate.

In fungi, the prenylation of aromatic substrates leads to an important class of secondary metabolites, the prenylated indole alkaloids. Also the fungal indole prenyltransferases are soluble enzymes without (N/D)DxxD motifs. Recently, we solved the first structure of a fungal indole prenyltransferase, i.e. of the dimethylallyltryptophan synthase (DMATS) and it also showed the PT barrel structure. Sequence similarity between DMATS and the above-mentioned bacterial prenyltransferases cannot be detected with PSI-BLAST searches but only with more powerful bioinformatics techniques like HHpred, indicating a distant evolutionary relationship.

Advances in the genetics and enzymology of aromatic prenylation reactions will be presented, including examples from the biosynthesis of aminocoumarin antibiotics, prenylated phenazines and prenylated naphthoquinone derivatives.