Pathways polyketide

Quinones represent a very large and heterogeneous class of biomolecules. Three major biosynthetic pathways contribute to the formations of various quinones. The aromatic skeletons of quinones can be synthesized by the polyketide pathway and by the shikimate pathway. The isoprenoid pathways are involved in the biosynthesis of the prenyl chain and in the formation of some benzoquinones and naphthoquinones. ... 

The Polyketide Pathway One metabolic process that has received much attention from natural product chemists is the production of secondary metabolites via polyketide synthase (PKS) enzymes. Polyketide synthases condense small starting... 

M Offenzeller, G Santer, K Totschnig, Z Su, H Moser, R Traber, E Schneider-Scherzer. Biosynthesis of the unusual amino acid (4R)-4-[(E)-2-butenyl]-4-methyl-L-threonine of cyclosporin A enzymatic analysis of the reaction sequence including identification of the methylation precursor in a polyketide pathway. Biochemistry 35 8401-8412, 1996. 

Metabolites of the phylum Porifera account for almost 50% of the natural products reported from marine invertebrates. Of the 2609 poriferan metabolites, 98% are derived from amino acid, acetogenin, or isoprenoid pathways. Isoprenoids account for 50% of all sponge metabolites, while amino acid and polyketide pathways account for 26% and 22%, respectively. A significant number of sponge metabolites appear to be derived from mixed biosynthetic pathways. Most structures reported containing carbohydrate moieties were glycosides. 

Of the more than 20,000 known species of lichens, only a few have been analyzed and identified as containing biologically active secondary compounds. Most of the unique secondary metabolites that are present in lichens are derived from the polyketide pathway, with a few originating from the shikimic acid and mevalonic acid pathways (Table 1.1). Previous studies have suggested that the para-depsides are precursors to mefa-depsides, depsones, diphenyl ethers, depsidones and dibenzofurans.9,12... 

In addition to those host nonselective toxins, Altemaria pathogens produce a number of host-selective toxins such as AK-toxin, AF-toxin, and ACT-toxin.298 9,10-Epoxy-8-hydroxy-9-methyldecatrienoic acid, the common backbone of these toxins, was biosynthesized via the polyketide pathway. Genetic approach has allowed the identification of a gene cluster for AF-toxin biosynthesis.299... 

Reductive cleavage and hydrolysis of appropriate diisoxazolylmethanes leads to 1,3,5,7-tetraketones, which can be used in the biomimetic synthesis of benzenoid compounds, which are formed in nature by the polyketide pathway. Some of these results are summarized in Table VIII. The synthesis of compounds such as (97) has provided a synthetic equivalent of a 1,3,5,7,9-... 

Figure 4.22 Combinatorial biosynthesis manipulation of the aromatic polyketide pathway.

Lovastatin and mevastatin are synthesized via polyketide pathways. Polyketides are a large group of structurally diverse secondary metabolites produced by bacteria, fungi, and plants. The factors influencing production of lovastatin or mevastatin have not been fuUy elucidated. Studies of Aspergillus terreus grown in chemically defined media indicate that... 

Aromatic natural products of polyketide origin are less prevalent in plants compared with microorganisms. The majority of the plant constituents that contain aromatic stmctures are known to arise from the shikimate pathway (see below). Unlike those derived from the shikimate pathway, aromatic products of the polyketide pathway invariably contain a meta oxygenation pattern because of their origin from the cyclization of polyketides. Phenolic compounds such as chrysophanol-anthrone (Bl), and emodin-anthrone (B2), and the anthraquinones, aloe-emodin (B3) and emodin (B4) (Fig. 2), are products of the polyketide pathway and are found to occur in some plants of the genera Cassia (Leguminosae) (21), Rhamnus (Rhamnaceae) (22), and Aloe (Liliaceae) (23). The dimer of emodin-anthrone (B2), namely hypericin, (B5) is a constituent of the antidepressant herbal supplement, St. John s wort (Hypericumperforatum, Hy-pericaceae) (24). 

Early feeding studies established that monensin A is biosynthesized from a classical polyketide pathway and is derived from five acetate, seven propionate, and one butyrate (for monensin B, an additional propionate unit replaces the butyrate) (7). Four of the nine oxygen atoms are derived from molecular oxygen, with the remaining five deriving from the corresponding carboxylic acid precursors (Fig. 2a). Based on these initial... 

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