Tenuazonic acid biosynthesis

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)... 

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). 

No information is available about the biochemical process which converts isoleucine and acetic acid (two units) into tenuazonic acid. By analogy with fatty acid and polyketide biosynthesis (cf. Turner, 1971), it is possible that an acetate (via acetyl coenzyme A) and a malonate unit (the monocoenzyme A derivative of malonic acid formed from acetyl-CoA and carbon dioxide) combine with the loss of a free carboxy group to give enzyme-bound aceto-acetic acid. Condensation of this activated keto acid with isoleucine would give rise to tenuazonic acid. This suggested process is analogous to the laboratory synthesis of a-acetyltetramic acids (Lacey, 1954). 

The mechanism of the conversion of Trp into cAATrp remains to be investigated. The biochemical process in this case may be similar to that suggested earlier for the biosynthesis of tenuazonic acid. The mechanism of the isoprenylation at the least nucleophilic position of the indole ring system of cAATrp has not as yet been elucidated. The corresponding isoprenylation of Trp in ergot alkaloid biosynthesis has received considerable attention (cf. Bellatti et al., 1977), but the mechanistic problem remains unsolved. 

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