Chalcone

Abstract: Chalcone synthase (CHS) is pivotal for the biosynthesis of flavonoid antimicrobial phytoalexins and anthocyanin pigments in plants. It produces chalcone by condensing one p-coumaroyl- and three malonyl-coenzyme A thioesters into a polyketide reaction intermediate that cyclizes. The crystal structures of CHS alone and complexed with substrate and product analogs reveal the active site architecture that defines the sequence and chemistry of multiple decarboxylation and condensation reactions and provides a molecular understanding of the cyclization reaction leading to chalcone synthesis. The structure of CHS complexed with resveratrol also suggests how stilbene synthase, a related enzyme, uses the same substrates and an alternate cyclization pathway to form resveratrol. By using the three-dimensional structure and the large database of CHS-like sequences, we can identify proteins likely to possess novel substrate and product specificity. The structure elucidates the chemical basis of plant polyketide biosynthesis and provides a framework for engineering CHS-like enzymes to produce new products.

Abstract: Chalcone is a unique template that is associated with several biological activities. In this review, an update of the cytotoxic and chemoprotective activities of chalcones is provided. Cytotoxicity against tumour cell lines may be the result of disruption of the cell cycle, inhibition of angiogenesis, interference with p53-MDM2 interaction, mitochondrial uncoupling or induction of apoptosis. Structural requirements for cytotoxic activity vary according to the mechanisms of action. For anti-mitotic activity, the presence of methoxy substituents, alpha-methylation of the enone moiety and the presence of 2' oxygenated substituents are favourable features. Conformational restraint of the chalcone template generally leads to a decrease in cytotoxic activity. Chemoprotection by chalcones may be a consequence of their antioxidant properties, mediated via inhibition or induction of metabolic enzymes, by an anti-invasive effect or a reduction in nitric oxide production. Hydroxyl and prenyl substituents are associated with antioxidant properties and induction of quinone reductase activities. The thiol reactivity of chalcones is likely to contribute to both cytotoxic and chemoprotective properties of these compounds.

Abstract: In most plants flower pigments derive from the flavonoid biosynthesis pathway. Consistent with this pathway in Petunia hybrida the key enzyme in flavonoid synthesis, chalcone synthase, is synthesized in the flower corolla, tube and anthers1. Here we show that constitutive expression of an 'anti-sense' chalcone synthase gene in transgenic petunia and tobacco plants results, with high frequency, in an altered flower pigmentation due to a reduction in levels of both the messenger RNA for the enzyme and the enzyme itself. The pattern of pigmentation varies among flowers of different transgenic plants, indicating that the activity of the anti-sense gene is influenced by DNA sequences that border its site of insertion in both a quantitative and a qualitative way. Backcrossing experiments show that the different pigmentation phenotypes resulting from the expression of anti-sense chalcone synthese gene(s) are stably inherited. These data establish that secondary metabolism in plants can be manipulated using transgenic plants that constitutively synthesize anti-sense RNA.