Evolution of aromatic prenyltransferases in the biosynthesis of indole derivatives

SHU-MING LI
Philipps-Universität Marburg
Institut für Pharmazeutische Biologie
Deutschhausstraße 17a
35032 Marburg
shuming.li@staff.uni-marburg.de
http://www.uni-marburg.de/fb16

Prenylated indole derivatives are a large class of alkaloids containing a tryptophan moiety substituted with isoprenic moieties at various positions of the indole nucleus, and are mostly found in fungi of the genera Aspergillus and Penicillium. Prenylation represents a critical step in the biosynthesis of these diverse structures and prenyltransferases are therefore very suitable for study of evolution of the metabolic diversity. Seven putative prenyltransferases showing significant sequence similarity to dimethylallyltryptophan synthase were found in the genome sequence of Aspergillus fumigatus by use of bioinformatic methods. Two of them, fgaPT1 and fgaPT2, belong to the biosynthetic gene cluster of fumigaclavine C (1, 2), an ergot alkaloid of clavine type. ftmPT1 and ftmPT2 are members of the biosynthetic gene cluster of fumitremorgins (3, 4). Two further genes, cdpNPT and 7-dmats are probably involved in the biosynthesis of prenylated cyclic dipeptides (5, 6). We have cloned the prenyltransferase genes, fgaPT1, fgaPT2, ftmPT1, cdpNPT and 7-dmats, and expressed them successfully in E. coli or/and Saccharomyces cerevisiae. The soluble enzymes were purified to near homogeneity and characterized biochemically (1-3, 4-6). Our bioinformatic and biochemical investigations have shown that the fungal prenyltransferases which catalyze the prenylation of the indole nucleus at different positions share significant sequence similarities with each other and have similar biochemical properties. These features are different to trans-prenyltransferases involved in the biosynthesis of terpenoids and to other known aromatic prenyltransferases which catalyze prenylation reactions of other aromatic substrates. In addition, these solube prenyltransferases showed broad substrate specificities towards aromatic substrates and can be used as tools for chemoenzymatic synthesis (7).

Literature:
1) Inge A. Unsöld und Shu-Ming Li (2005) Microbiology 151: 1499-1505.
2) Inge A. Unsöld and Shu-Ming Li (2006) ChemBioChem 7:158-164.
3) Alexander Grundmann and Shu-Ming Li (2005) Microbiology 151: 2199-2207.
4) Shubha Maiya, Alexander Grundmann, Shu-Ming Li and Geoffrey Turner (2006) ChemBioChem, 7: 1062-1069.
5) Wen-Bing Yin, Han-Li Ruan, Lucia Westrich, Alexander Grundmann and Shu-Ming Li (2007). ChemBioChem, in press
6) Anika Kremer, Lucia Westrich and Shu-Ming Li (2007) Microbiology, in press
7) Nicola Steffan Inge A. Unsöld Shu-Ming Li (2007) ChemBioChem, in press

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