Tetramic acids, biosynthesis

Investigations of the biosynthesis of three tetramic acids, namely, tenua-zonic acid (1), erythroskyrin (3), and aCA (4), indicated that the primary step of tetramic acid biosynthesis involves the condensation of an amino acid (L-isoleucine, valine, and L-tryptophan, respectively) with an acetate-derived polyketide [(acetoacetic acid in the case of (1) and (4), a C20 poly-ketide in the case of (3)]. The details of the polyketide assembly and the... 

It is somewhat surprising to find that there have been only three published reviews on tetramic acids. The first reports on the advances in tetramic acid chemistry up to 1993 [1], another describes the synthesis of tetramic acid antibiotics [3], and a third, dealing with the structure, isolation and synthesis of naturally occurring tetramic acids, was published in 1995 [4]. The present review is an attempt to cover the field of tetramic acid metabolites with particular emphasis on the structure, biosynthesis and biological activity of these compounds. 

The biosynthesis of tenuazonic acid was studied using [l-14C]-labeled acetate. N-acetoacetyl-L-isoleucine (7) was detected by radioactive trapping, indicating that amide formation, rather than carbon-carbon bond formation is probably the first step. None of the simple tetramic acid (8)... 

The Biosynthesis of Polyketides, Tetramic Acids, and Pyridones in Fungi... 

Holzapfel, C. W. The biosynthesis of cyclopiazonic acid and related tetramic acids. In The Biosynthesis of Mycotoxins (P. S. Steyn, ed.), pp. 327-355, Academic Press, New York 1980... 

In the proposed scheme of the biosynthesis of cytochalasins A (25) and B (26), outlined in Fig. 14, the amide linkage of the nonaketide 53 to phenylalanine (46) may be regarded as the initial step. The subsequent condensation of the amide 54 leads to the five-membered ring of the y-lactam 55, which is a derivative of tetramic acid. One of the carbonyl groups of y-lactam 55 reacts with the penultimate carbon atom of the ketide after reduction to the intermediate 56, with formation of the bond between C(4) and C(5). Partial reductions and water eliminations yield the bicyclic intermediate 58, in which the bond between C(8) and C(9) is transformed by condensation. By an... 

As a result of the real and potential importance of the tetramic acids as mycotoxins, their chemistry and biochemistry have received considerable attention. In this chapter, studies on the biosynthesis of cyclopiazonic acid and related tetramic acids will be reviewed. 

Tenuazonic acid was the first tetramic acid whose biosynthesis received attention (Stickings and Townsend, 1961). A strain oiA. tenuisKuci. growing on Czapek-Dox medium has been shown to incorporate more than 4% of the from added sodium [1- C]acetate into tenuazonic acid (1). 

The Biosynthesis of Cyclopiazonic Acid and Related Tetramic Acids CEDRIC W. HOLZAPFEL... 

Most known thiamin diphosphate-dependent reactions (Table 14-2) can be derived from the five halfreactions, a through e, shown in Fig. 14-3. Each halfreaction is an a cleavage which leads to a thiamin- bound enamine (center, Fig. 14-3) The decarboxylation of an a-oxo acid to an aldehyde is represented by step b followed by a in reverse. The most studied enzyme catalyzing a reaction of this type is yeast pyruvate decarboxylase, an enzyme essential to alcoholic fermentation (Fig. 10-3). There are two 250-kDa isoenzyme forms, one an a4 tetramer and one with an ( P)2 quaternary structure. The isolation of ohydroxyethylthiamin diphosphate from reaction mixtures of this enzyme with pyruvate52 provided important verification of the mechanisms of Eqs. 14-14,14-15. Other decarboxylases produce aldehydes in specialized metabolic pathways indolepyruvate decarboxylase126 in the biosynthesis of the plant hormone indoIe-3-acetate and ben-zoylformate decarboxylase in the mandelate pathway of bacterial metabolism (Chapter 25).1243/127... 

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