Benzophenone synthase

BEERHUES, L., Benzophenone synthase from cultured cells of Centaurium erythraea, FEBSLett., 1996,383,264-266. 

Fig. 1 Biosynthesis of plant polyphenols by CHS-superfamily type III PKSs. CHS chalcone synthase STS stilbene synthase ACS acridone synthase VPS valerophenone synthase SPS styrylpyrone synthase BPS benzophenone synthase OAS olivetolic acid synthase 2PS 2-pyrone synthase BAS benzalacetone synthase CUS curcumin synthase...

Benzophenone synthase (BPS) and biphenyl synthase (BIS) catalyze the formation of the same linear tetraketide from benzoyl-CoA and three molecules of malonyl-CoA. However, BPS cyclizes this intermediate via intramolecular C6-+C1 Claisen condensation, whereas BIS uses intramolecular C2— C7 aldol condensation. Benzophenone derivatives include polyprenylated polycyclic compounds with hi pharmaceutical potential. Biphenyl derivatives are the phytoalexins of the economically important Maloideae. 

Type III polyketide synthases (PKSs) generate a diverse array of natural products by condensing multiple acetyl units from malonyl-CoA to specific starter substrates (1,2). The homodimeric enzymes orchestrate a series of acyltransferase, decarboxylation, condensation, cyclization, and aromatizatidn reactions at two functionally independent active sites. Due to their ability to vary either the starter molecule or the type of cyclization and the number of condensations, they are, along with terpene synthases, one of the major generators of carbon skeleton diversity in plant secondary metabolites (i). Among the starter substrates used, benzoyl-CoA is a rare starter molecule. It is utilized by bacterial type I PKSs to form soraphen A, enterocin and the wailupemycins (4). in plants, benzoyl-CoA is the starter unit for two type III PKSs, benzophenone synthase (BPS) and biphenyl synthase (BIS), both of which were cloned in our laboratory. 

Further investigation of xanthone biosynthesis was carried out by Beer-hues with the detection of an enzyme named benzophenone synthase from cultured cells of Centaurium erythraea [34], The formation of 2,3, 4,6-tetrahydroxybenzophenone, which is a central step in xanthone biosynthesis, was shown in cell-free extracts from cultured cells of C. erythraea (Fig. 4). 

As part of their continuing study the same research group have reported the detection and partial characterization of another enzyme named benzophenone 3 -hydroxylase, leading to the formation of 2,3, 4,6-tetrahydroxy-benzophenone in cultured H. androsaemum cells as well as benzophenone synthase. In contrast to the enzyme from C. erythraea, benzophenone synthase from H. androseamum acts more efficiently on benzoyl CoA than 3 -hydroxybenzoyl CoA which is supplied by 3-hydroxybenzoate CoA lig-ase [35]. In C. erythraea, 2,3, 4,6-tetrahydoxybenzophenone is converted to... 

Previous researchers have suggested [6,8] that benzophenones are biosynthesized by condensation of metabolites from the shikimate pathway, forming the A-ring, and the acetate-malonate pathway, creating the B-ring. This produces the basic 13-carbon benzophenone skeleton, Fig. (1). Support for this biosynthetic pathway includes the isolation of benzophenone synthase from Centaurium erythraea [9] and research by Atkinson etal. [10] who examined benzophenones as intermediates in the synthesis of xanthones. (Xanthone biosynthesis is reviewed by... 

Shi S-P, Wanibuchi K, Morita H, Endo K, Noguchi H, Abe I (2009) Enzymatic formation of unnatural novel chalcone, stilbene, and benzophenone scaffolds by plant type III polyketide synthase. Org Lett 11 551-554... 

The isomeric products of the xanthone synthases are the precursors of the majority of plant xanthones (77). This class of secondary metabolites also includes prenylated compounds with high pharmaceutical potential. Gambogic acid is a bridged polycyclic derivative that induces apoptosis independent of the cell cycle through a novel mechanism of caspase activation (22). Rubraxanthone inhibits methicillin-resistant strains of Staphylococcus aureus 23). Its activity compares to that of the antibiotic vancomycin. Bioactive complex benzophenone derivatives may serve as potential lead compounds for designing drugs. Synthetic approaches to these fascinating structures have recently been developed 24,25). 

Flavonoids serve as flower pigments, UV protectants, phytoalexins and signal molecules (1,2). Unlike BPS, CHS exhibits a broad substrate specificity (Table I). H. androsaemum CHS and the enzymes from other sources (27) accepted CoA-linked benzoic acids as minor subshates and formed the respective benzophenones. An efficient but unphysiological starter unit is benzoyl-CoA for 2-pyrone synthase (2-PS) that performs only two decarboxylative condensations with malonyl-CoA to produce 6-phenyl-4-hydroxy-2-pyrone (28). In cell cultures of H. androsaemum, benzoic acid originates from cinnamic acid by side-chain degradation (29). The underlying mechanism is CoA-dependent and non-) -oxidative. The complete sequence of enzymes involved was detected. 

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