Biosynthesis of biphenyls and benzophenones - Evolution of benzoic acid-specific polyketide synthases in plants
LUDGER BEERHUES
Institut für Pharmazeutische Biologie
Technische Universität Braunschweig
Mendelssohnstraße 1
D-38106 Braunschweig
l.beerhues@tu-bs.de
http://www.ipb-bs.de
In plants and microorganisms, polyketide synthases (PKSs) form an impressive diversity of natural products. These compounds include benzophenone and biphenyl derivatives which occur in the plant families Clusiaceae and Rosaceae, respectively. The carbon skeleton of either class of compounds is formed by a type III PKS which uses the rare starter substrate benzoyl-CoA and catalyzes its condensation with three malonyl-CoAs to give a linear tetraketide. This intermediate undergoes different intramolecular cyclizations in the active sites of benzophenone synthase and biphenyl synthase, which raises the question as to the evolution of these two novel PKSs and their reaction mechanisms. Both enzymes were cloned and functionally expressed. Rationalized by homology modeling, active site residues were mutagenized, leading to altered substrate and product specificities. To gain more insight into structure-function relationships, both enzymes are being crystallized in cooperation with the Stubbs group, Halle. Cloning of a cDNA encoding the functionally related enzyme, biphenylcarboxylate synthase, is under way and the evolutionary relationship of this enzyme to type III PKSs will be studied.
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