Biosynthesis of phenolic acids

FIGURE 10.5 Biosynthesis of phenolic acids. (Adapted from Duthie, G. and Crozier, A., Curr. Opin. Lipid, 11,43, 2000 Hakkinen, S., Flavonols and phenolic acids in berries and berry products. Doctoral dissertation, Kuopio University Publications, Kuopio, Finland, D. Med. ScL, 221, 92, 2000.)... 

It is now known that the mode of biosynthesis of phenolic acids and related phenols strongly resembles that of fatty acids universally found in nature. Both classes of compound are assembled by multienzyme complexes catalyzing condensation reactions between acyl and malonyl residues. The formation of phenols usually entails few reductive steps, in contrast to fatty acid synthesis, and the oxygen functions are therefore retained. 

Fig. 63.3 Pathway of the shikimic acid in the biosynthesis of phenolic acids...

The shikimate pathway is the major route in the biosynthesis of ubiquinone, menaquinone, phyloquinone, plastoquinone, and various colored naphthoquinones. The early steps of this process are common with the steps involved in the biosynthesis of phenols, flavonoids, and aromatic amino acids. Shikimic acid is formed in several steps from precursors of carbohydrate metabolism. The key intermediate in quinone biosynthesis via the shikimate pathway is the chorismate. In the case of ubiquinones, the chorismate is converted to para-hydoxybenzoate and then, depending on the organism, the process continues with prenylation, decarboxylation, three hydroxy-lations, and three methylation steps. - ... 

Tetraacetic acid (or a biological equivalent) is suggested as an intermediate in the biosynthesis of phenolic natural products. In the laboratory, it can be readily converted to orsellinic acid. Suggest a mechanism for this reaction under the conditions specified. 

It therefore appeared that a general mechanism for enzymatic esterification of phenolic acids with glucose was operative, whereas the reaction with other alcoholic moieties proceeded via carboxyl-activated acyl derivatives. [In this context it should be emphasized that glucose esters must not be confused with glucosides different enzymes are involved in the biosynthesis of these two types of phenolic glucose derivatives (36)]. 

An exemplary investigation of the biosynthesis of multicolic acid by fungi (from acetate via phenolic intermediates) made full use of H NMR spectra with LIS shifts and I3C spectra obtained for substrates enriched by [1-13C]-, [2-13C]- and [l,2-13C]-acetate (79MI31006). The 13C chemical shifts are shown with structure (150) the lJ values for the heavy bonds show intact acetate residues and are 48 Hz for the single bond and 90 Hz for... 

C-Methylation also features in the biosynthesis of usnic acid (Figure 3.41), an antibacterial metabolite found in many lichens, e.g. Usnea and Clado-nia species, which are symbiotic combinations of alga and fungus. However, the principal structural modification encountered involves phenolic oxidative coupling (see page 28). Two molecules of methylphloracetophenone are incorporated, and these are known to derive from a pre-aromatization methylation reaction and not by... 

Information on the biosynthesis of the phenolic glycolipids is very limited.220 The carbon atoms in the methyl-branched structures in mycocerosic acids are derived from propanoate.221-222 So also are those in phthiocerol.223 224 The aromatic ring can be derived from tyrosine.224 The methoxyl residue in phenolphthiocerol presumably comes from methionine, by analogy with the known source in the related lipid phthiocerol.225 226 Rainwater and Kolatukuddy226 demonstrated two steps in the biosynthesis of mycocerosic acids, and isolated the enzymes involved, but the biosynthetic steps leading to phenolphthiocerol itself are not known. 

Merely by writing ketones instead of phenols and doing one disconnection corresponding to a simple carbonyl condensation, we have reached a possible starting material which is a typical acyl polymalonate product without any reductions. This is what polyketides are. The fatty acids are assembled with full reduction at each stage. Polyketides are assembled from the same process but without full reduction indeed, as the name polyketide suggests, many are made without any reduction at all. This is the biosynthesis of orsellinic acid. 

Packter, N.M. Studies on the Biosynthesis of Phenols in Fungi. Production of 4-Methoxytoluquinol, Epoxysuccinic Acid and a Diacetylenic Alcohol by Surface Cultures of Lentinus degener I.M.I. 110525. Biochem. J. 114, 369 (1969). 

This chapter will present an account of the biosynthesis of phenols, with emphasis on the enzymology of the processes involved, and draw analogies between the reaction sequences responsible and those concerned with fatty acid synthesis. It makes no attempt to cover the chemistry of these metabolites exhaustively. 

Against this backcloth it is perhaps not surprising to learn, that, despite its distinctive position in the overall patterns of plant phenol metabolism, ambiguity still surrounds the biosynthesis of gallic acid. Several pathways have been proposed. Zenk formulated a conventional pathway (Fig. 7, a) from L-phenylalanine to 3,4,5-trihydroxy-cinnamic acid followed by 6-oxidation to give gallic acid. 

The possible pathway for the biosynthesis of benzoylacetic acid as building block of phenolic side chain is the following (Fig. 11.18). Phenylalanine is converted into trans-Cinnamic acid by the enzyme phenylalanine ammonia-lyase (PAL). Hydroxylation of Cinnamic acid gave 3-hydroxy-3-phenylpropanoic acid which is transformed to benzoylacetic acid by (3-oxidation (chain degradation). 

Harris TM, Carney RL (1967) Synthesis of 3,5,7-triketo acids and esters and their cyclizations to resorcinol and phloroglucinol derivatives. Models of biosynthesis of phenolic compounds. J Am Chem Soc 89 6734-6740... 

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