Multicolic acid

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... 

In a major study of the biosynthesis of multicolic acid from acetate by Penicillium multicolor, Gudgeon, Holker, and Simpson made excellent use... 

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 relatively high incorporations of tracer molecules into secondary metabolites in micro-organisms has enabled detailed studies to be made of the biosynthesis of the fungal metabolites patulin (10) and multicolic acid (79). Carbon-14 work has demonstrated the polyketide origin of patulin, and the biosynthesis of multicolic acid from acetate has been studied by C-n.m.r. spectroscopy. The biosynthesis of patulin has been investigated extensively at the enzymology level. In the first... 

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. 

In one of the first demonstrations of the use of doubly C-labelled acetate in a biosynthetic problem, Holbcer and co-workers 82) have shown that the biosynthesis of multicolic acid (79) in Penicillium multicolor proceeds via oxidative cleavage between C-4 and C-5 of the poly-ketide derived aromatic acid (191). From 1,2- C-acetate feedings, and the magnitudes of the C- C-couplings in the C-n.m.r. spectra of the metabolite, it was established that the acetate residues C-2—C-5, C-6—C-7, C-8—C-9 and C-4—C-10 were incorporated intact into the acid (Scheme 17). These data are only compatible with a biosynthetic origin by oxidative cleavage of the polyketide derived aromatic precursor (191). 

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). 

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