Muconic acid 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 ... 

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. 

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. 

Catalyzed conversion of D-glucose into c/s, c/s-muconic acid (27) required creation of a biosynthetic pathway not known to exist naturally (Figure 5). This pathway relied on DHS dehydratase (Figure 5, enzyme A) (44,45) to couple aromatic biosynthesis to... 

FIGURE 19.6 The two branches of the P-ketoadipate pathway, which comprise catechol and protocatechuic acid as central metabolites (Harwood and Parales, 1996). To obtain cis,cis-muconic acid its further conversion has to be blocked. Additionally, other small aromatic compounds are converted via different pathways of which phenyl acetic acid and homogentisic acid are central metabolites (Jimenez et al., 2002). 

Total Oxidation of Tryptophan. Certain microorganisms that use tryptophan as a primary food modify the pathway described above. The scheme used by these organisms involves the formation of anthranilic acid by the reactions already described. In an unknown manner, anthranilic acid is oxidized to catechol. Catechol is oxidized to m,cts-muconic acid by pyrocatechase. This is an oxygenase that was shown to be... 

Though the muconic acid isolated from benzene cultures very likely originates by oxidative cleavage of catechol, the actual formation of catechol from benzene by bacteria has not been demonstrated. Its place in this pathway is circumstantial and can only be inferred. Two possibilities could account for its formation, namely, successive oxygenations (mono-hydroxylations) or simultaneous dihydroxylation. In the first, phenol would be involved, a possibility stemming from the fact of biological conversion of benzene to phenol in rabbits (Porteus and Williams, 1949). The first pathway would be represented as Eq. (8). 

Figure 5. The biocatalytic pathway (boxed arrows) created for microbial conversion of D-glucose into cis, cw-muconate from the perspective of the biochemical pathways from which the enzymes were recruited. Conversion of D-glucose into DHS requires transketolase (tkt) from the pentose phosphate pathway and DAHP synthase (aroF, aroG, aroH)y DHQ synthase aroB and DHQ dehydratase aroD) from the common pathway of aromatic amino acid biosynthesis. Conversion of DHS into catechol requires DHS dehydratase (aroZ, enzyme A) from hydroaromatic catabolism, protocatechuate decarboxylase aroY, enzyme B), and catechol 1,2-dioxygenase (caM, enzyme C) from the benzoate branch of the p-ketoadipate pathway. (Adapted and reproduced with permission from ref. 21.)...

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