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Cytotoxic tetramic acid derivative produced by a plant type-III polyketide synthase

, : Cytotoxic tetramic acid derivative produced by a plant type-III polyketide synthase. Journal of the American Chemical Society 133(13): 4746-4749

The tetramic acid (2,4-pyrrolidinedione) scaffold has been recognized as an important structural feature because of its mycotoxic, antibacterial, antiviral, and antioxidant activities. This important class of natural products is reportedly produced by the type-I polyketide synthase/nonribosomal peptide synthetase (PKS/NRPS) hybrid megaenzyme systems. In contrast, the benzalacetone synthase (BAS) from Rheum palmatum is a structurally simple, plant-specific type-III PKS that catalyzes the one-step decarboxylative condensation of malonyl-CoA with 4-coumaroyl-CoA. The type-III PKS exhibits unusually broad substrate specificity and notable catalytic versatility. Here we report that R. palmatum BAS efficiently produces a series of unnatural, novel tetramic acid derivatives by the condensation of malonyl-CoA with aminoacyl-CoA thioesters chemically synthesized from L- and D-amino acids. Remarkably, the novel tetramic acid dimer D-5 formed from D-phenylalanoyl-CoA showed moderate antiproliferative activity against murine leukemia P388 cells.


PMID: 21391603

DOI: 10.1021/ja2006737

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