Polyketides and lipids

Of the four major classes of biochemicals (carbohydrates, proteins, nucleic acids and lipids), experiments have shown that the first three classes could have arisen through prebiotic chemistry. Although the biosynthesis of many natural products can be traced back to acetate (e.g. fatty acids, terpenes and polyketide biosynthesis) or amino acids (e.g. alkaloid biosynthesis), there are many whose biosynthetic origins are either obscure or result from a complex combination of pathways (Fig. 2). 

Is a specific Inhibitor of type II fatty acid synthetase In higher plants and . coll 12401. The acetyl-CoA ACP S-acety1-transferase Is the apparent specific site of Inhibition 12411. Another antibiotic, cerulenin (structure not shown) Inhbits -ketococy1-ACP synthetase I In bacteria, fungi, and plants, but also Is Inhibitory to other sites such as polyketide and sterol biosynthesis 1242-2441. Cerulenin and thiolactomycin Inhibited CQ14W-acetate Incorporation Into fatty acids at 150 values of 50 and 4 uM, respectively 12451. Recently cydohexanedlone herbicides have been shown to Inhibit lipid biosynthesis by Inhibition of acetyl-CoA carboxylase 12461. 

The squalestatins, e.g. 6.28, also known as the zaragozic adds, have attracted considerable interest as inhibitors of squalene synthase and hence of cholesterol biosynthesis and lipid deposition in the circulatory system. They are also inhibitors of farnesyl protein transferase and thus they may have other potentially useful biological applications. They are formed by Phoma spedes and also by Setosphaeria khartoumensis. The squalestatins are characterized by a dioxabicyclo-octane core bearing three carboxyl groups and two polyketide chains, one of which is attached as an ester. The biosynthetic incorporation of succinic acid into part of the bicyclo-octane, together with its oxygenation pattern, indicate that it may be derived via oxaloacetic acid. Both the polyketide chains have several pendant methyl groups attached to them, which arise from methionine, whilst benzoic add ads as a starter unit for one of the chains. These complex structures are thus the summation of several biosynthetic pathways. 

These are called acetogenins (or sometimes polyketides) and many are antibiotics. Many of these compounds are aromatic and their pathway of formation is the principal means of synthesis of the benzene ring in nature. Not all are lipids, because partial reduction often leaves oxygen-containing groups that render the product soluble in water. 

Packter, N. M., Biosynthesis of acetate-derived phenols (polyketides), in Lipids Structure and Function (P. K. Stumpf ed.). 

Lipids Fatty Acids, Acyltunichlorins, Polyketides, and Oxylipins... 

The main metabohtes produced by Monascus are polyketides formed by the condensation of one acetylcoA with one or more malonylcoAs with a simultaneous decarboxylation as in the case of lipidic synthesis. They consist of the pigments, monacohns, and under certain conditions a mycotoxin. 

Until recently no enzymes able to produce olivetol-like compounds have been isolated. In an article by Puna et al., polyketide III enzymes were responsible for the formation of phenohc lipid compound [34], a natural product group that ohvetol belongs to. Although the biosynthesized compounds contained a longer chain, which increased over time, the study supported the hypothesis of olivetohc acid production by a polyketide III synthase. Further studies on the genetic and protein level are essential to elucidate the mode of mechanism by which olivetohc acid is formed in C. sativa. 

Polyketide synthase enzyme assays contained 100 mM potassium phosphate buffer (pH 7.0), 40 pM malonyl-CoA, 25 pM starter molecule (i.e. palmitoyl-CoA), and 2 pg protein in a 200 pL volume at 30° C for 30 minutes. Reactions were quenched by addition of 10 pL of 20% HCl. The lipid resorcinol products were extracted by phase partitioning with 1 ml of ethyl acetate. The organic phase (upper layer) obtained by centrifugation at -14,000 x g for 1 minute was transferred to a fresh tube, dried under vacuum, and subsequently analyzed by GC/mass spectrometry as a trimethysilyl derivative. Product formation was quantified using selected ion monitoring at m/z 268, a common fragment to all... 

The combination of a root hair specific EST approach and expression analysis was an effective strategy for isolating candidate polyketide synthases potentially involved in sorgoleone biosynthesis. As a result of these efforts, two novel type III polyketide synthases have been identified that preferentially use long chain acyl Co-A s and are potentially involved in sorgoleone biosynthesis. These candidate polyketide synthases can form pentadecatriene resorcinol, an intermediate in sorgoleone biosynthesis. Furthermore, these efforts may aid in the identification of other polyketide synthases responsible for the biosynthesis of phenolic lipids in other plant species. 

As seen in figure 1, carbohydrates are degraded to pyruvic acid, which is oxidised to acetate in a form which can condense to form fatty acids and polyketides (includes aromatic benzenoid molecules). Fatty acids react with glycerol to give fats or lipids. A different biosynthetic pathway leads from acetate via the condensation product mevalonic acid to mono-, sesqui- and diterpenes which are ingredients... 

Lipids and polyketides are biosynthesized by aldol-type reactions of esters with coenzyme-A, as shown in Scheme 3.2. The coenzyme-A ester of a fatty acid undergoes reaction with acetyl coenzyme-A to give... 

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