Tetronic acids biosynthesis

Bentley, R., and J. G. Keil Tetronic Acid Biosynthesis in Molds II. Formation of Penicillic Acid in Penicillium cyclopium. J. Biol. Chem. 237, 867 (1962). 

C(3). Two possibilities remain for the sequence in which the biogenetic units are joined together. The first involves condensation of valine with a C2o-polyketide. The other possibility involves the condensation of a Cig-polyketide with a five-membered ring formed from valine and one malonate unit. Similar possibilities, but with a C4-dicarboxylic acid replacing valine, have been considered by Bentley et al. (1962) for tetronic acid biosynthesis in Penicillium charlessi. 

Incorporations of [ 2] acetate have also enabled the detection of bond cleavage and skeletal rearrangement processes occurring during the biosynthesis of a wide range of metabolites. One of the earliest examples was in the biosynthesis of multicolic acid (26) and related tetronic acid metabolites of Penicillium multicolor [21]. The observation of couplings and, more... 

Not all fungal tetronic acids are derived by this pathway. The biosynthesis of multicolic acid (6.17), a metabolite of P. multicolor, has been shown by carbon-13 labelling experiments to follow entirely a polyketide pathway. The proposed biosynthetic pathway (Scheme 6.2) involves the intermediacy of a 6-pentylresorcylic acid (6.16) and the cleavage of an aromatic ring. 

The fungal metabolites patulin (10) and multicolic acid (79) are derived in nature via oxidative cleavages of polyketide derived aromatic intermediates a similar pathway has been established for the tetronic acid penicillic acid (185). By contrast, the biosynthesis of carolic acid (76a) which is found with dehydrocarolic acid (75) in P. charlesii, has been shown to occur from Krebs cycle intermediates. 

The biosynthesis of the fungal tetronic acids penicillic acid (185) and carolic acid (76 a), which are closely related structurally to patulin and multicolic acid, have also been studied extensively. Early work with " C-labelled precursors has clearly demonstrated the polyketide origin of penicillic acid, and also the intermediacy of orsellinic acid... 

The biosynthesis of the fungal tetronic acid carolic acid (76 a) in Penicillium charlesii is markedly different from that of patulin, multicolic acid and penicillic acid. Carbon-14 work has demonstrated that the carbon sub-unit C-3, C-4, C-9 in the acid is derived from a C-4-dicarboxylic acid such as succinate, whereas the remaining six carbons (C-1, C-2, C-5, C-6, C-7, C-8) are derived from two malonate units (C-5, C-6, C-7, C-8) and just one acetate unit (C-1, C-2) (Scheme 19) (775). It is proposed then that the biosynthesis of carolic acid proceeds from a C4-dicarboxylic acid first to either y-carboxymethyltetronic acid (196) or to carlosic acid (77 b) hydroxylation of carlosic acid then gives rise to carlic acid (77 a) which on decarboxylation produces carolic acid 176). 

Gudgeon, J. A., J. S. E. Holker, and T. J. Simpson Use of Singly and Doubly Labelled C-Acetate in the Elucidation of the Structures and Biosynthesis of Multicolic and Multicolosic Acids, New Tetronic Acids from Penicillium multicolor. Chem. Commun. 636(1974). 

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