Muconate pathways

Hydroxylation and dioxygenation are not, however, mntnally exclusive, because the toluene dioxygenase from Pseudomonasputida FI hydroxylates both phenol and 2,5-dichloro-phenol with the introduction of only one atom of oxygen (Spain et al. 1989). Snbsequent degradation by dioxygenation follows established pathways in which chloride is eliminated from muconic acids after ring fission. 

Surface Water. Aniline degraded in pond water containing sewage sludge to catechol, which then degrades to carbon dioxide. Intermediate compounds identified in minor degradative pathways include acetanilide, phenylhydroxylamine, as,cA-muconic acid, p ketoadipic acid, levulinic acid, and succinic acid (Lyons et al, 1984). 

Exceptions exist to this tendency for ready incorporation of the initial transformation products of xenobiotic compounds into a common pathway. First, occasionally a product is formed which is unreactive in subsequent steps in a particular microorganism. Such partially degraded compounds have been referred to as dead-end metabolites (Knackmuss, 1981). An example of this is the 5-chloro-2-hydroxy-muconic acid semialdehyde produced by the meta cleavage of 4-chlorocatechol by a particular pseudomonad species ... 

Another enzyme of the mandelate pathway of degradation of aromatic rings (Fig. 25-8) is the cis,cis-muconate lactonizing enzyme which catalyzes the reaction of Eq. 13-23. It has a three-dimensional struc-... 

The mandelate and jS-ketoadipate pathways serve as an example of gene duplication, as there is strong evidence pointing to the former evolving from the latter. Evolution of mandelate racemase from muconate lactonizing enzyme points to the relevance of the enzyme mechanism for catalytic reactivity. 

The integrated dose to a tissue over a 14-hour period (6-hour exposure, 8 hours following exposure) was calculated for benzene metabolites in Fischer 344 rats and B6C3Fj mice that were exposed to 50 ppm of radiolabeled (3H) benzene (Sabourin et al. 1988). The major metabolic products in rats were detoxification products that were marked by phenyl conjugates. In contrast, mice had substantial quantities of the markers for toxification pathways (muconic acid, hydroquinone glucuronide, and... 

Isomerases catalyze conversions within one molecule. For example, the cis.cis-muconate lactonizing enzyme (cycloisomerase) catalyzes the chiral conversion of ds,cis-muconic acid to (K)-muconolactone (Fig. 29). It is a key enz)one in the degradation of benzoate via the p-ketoadipate pathway (109). Chiral lactones could be useful as chiral synthons. 

Scheme 24.1 Possible pathways for the solid-state photoreactions of benzyl (Z,Z)-muconates.

Degradation of catechol and 3,4-dihydroxybenzoate — The key observation was that the ring-cleavage product of catechol or 3,4-dihydroxybenzoate was P-ketoadipate that is formed by a series of lactonizations and rearrangements. The various steps were elucidated using pure samples of the proposed intermediates and enzyme preparations to study induction patterns. Mutants were then used to elucidate the regulation of the pathways cis,cis-muconate is the inducer for the catechol pathway, and P-ketoadipate for the 3,4-dihydroxybenzoate pathway (Ornston 1966). 

The X-ray crystal structure of P. putida muconate lactonizing enzyme (cycloisomerase) was determined in 1987, and was found to contain an a/(i barrel fold, also found in triosephosphate isomerase and enolase. Remarkably, the structure of P. putida mandelate racemase, which catalyzes a mechanistically distinct reaction earlier in the same pathway, was found in 1990 to have a homologous structure, indicating that the structural fold of the enolase superfamily is able to support a range of enzyme-catalyzed reactions. The P. putida 3-carboxy- r, x-muconate lactonizing enzyme, in contrast, shares sequence similarity with a class II fumarase enzyme, and determination of its structure in 2004 has shown that it shares the same fold as the class II fumarase superfamily, hence these two catalysts of similar reactions have evolved from different ancestors. ... 

The Cope-like ring closure to 19 is not the only feasible thermal rearrangement pathway for muconaldehyde. Vogel noted the utility of entering the muconate series via ring opening of cyclobutene-3,4-dicarboxylates [55]. Indeed, the isomerization of 20c to 20a (Eq. 2) is known to proceed through cyclobutene 21b [56]. The... 

Four billion pounds of adipic acid are produced each year using petroleum-based feedstocks, carcinogenic benzene as starting material, and extreme reaction conditions. Nitrous oxide, which plays a role in ozone layer depletion, is emitted as a byproduct. As an alternative to the currently employed synthetic methcdology, a two-step synthesis of adipic acid from D-glucose has been developed which eliminates each of these problems. A microbial catalyst was created which possesses a novel biosynthetic pathway that synthesizes cis, cis-muconic acid from D-glucose. This pathway does not occur in nature but has been created in a strain of Escherichia colL Cis, cw-muconic acid is exported to the culture supernatant, where it is hydrogenated under mild conditions to yield adipic acid. 

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