Applied Microbiology and Biotechnology, Vol.84, No.4, 631-639, 2009
Applications of dimethylallyltryptophan synthases and other indole prenyltransferases for structural modification of natural products
A series of putative indole prenyltransferase genes could be identified in the genome sequences of different fungal strains including Aspergillus fumigatus and Neosartorya fischeri. The gene products show significant sequence similarities to dimethylallyltryptophan synthases from various fungi. These genes belong to different gene clusters and are involved in the biosynthesis of secondary metabolites. Ten of them were cloned and overexpressed in Escherichia coli and Saccharomyces cerevisiae and proven to be soluble proteins. They catalyse different prenyl transfer reactions onto indole moieties of various substrates and do not require divalent metal ions for their prenyl transfer reactions. These enzymes showed broad substrate specificities towards their aromatic substrates. Diverse simple tryptophan derivatives and tryptophan-containing cyclic dipeptides were accepted by several prenyltransferases as substrates and converted to prenylated derivatives. This feature of substrate flexibility was successfully used for regiospecific and stereospecific synthesis of different indole derivatives.
Keywords:Aspergillus;Neosartorya;Chemoenzymatic synthesis;Indole alkaloid;Cyclic dipeptide;Diketopiperazine;Prenyltransferase;Dimethylallyltryptophan synthase;Indole derivatives