P-ketoadipate pathway

Parke D, LN Ornston (1986) Enzymes of the P-ketoadipate pathway are inducible in Rhizobium and Agrobacterium spp. and constitutive in Bradyrhizobium spp. J Bacteriol 165 288-292. 

Harwood CS, RE Parales (1996) The P-ketoadipate pathway and the biology of self-identity. Annu Rev Microbiol 50 553-590. 

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. 

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.)...

Stanier RY, Omston LN (1973) P-Ketoadipate pathway. Adv Microb Physiol 9 89-151 Subramanian V, Liu TN, Yeh WK, Gibson DT (1979) Toluene dioxygenase purification of an iron-sulfur protein by affinity chromatography. Biochem Biophys Res Commun 91 1131-1139 Subramanian V, Liu TN, Yeh WK, Serdar CM, Wackett LP, Gibson DT (1985) Purification and properties of ferredoxin Q a component of toluene dioxygenase from Pseudomonas putida FI. J Biol Chem 260 2355-2363... 

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). 

Figure 3.10. Catabolism of quinate and shikimate by the p-ketoadipate pathway in micro-organisms " ...

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). 

ALAS is the initial enzyme of the pathway and catalyzes the formation of ALA from succinyl-CoA and glycine. The enzyme is mitochondrial and requires pyridoxal phosphate as a cofactor, which forms a Schiff base with the amino group of glycine at the enzyme surface. The carbanion of the Schiff base displaces Co enzyme A from succinyl-CoA with the formation of a-amino-P-ketoadipic acid, which is then... 

Classic studies were devoted to the regulation of the enzymes for conversion of catechol and protocatechuate to (l-ketoadipate by Pseudomonas putida (Om-ston 1966), the [f-ketoadipate pathway in Moraxella calcoacetica (Canovas and Stanier 1967), and the mandelate pathway in P. aeruginosa (Rosenberg 1971). All of these organisms cleave the catechol by intradiol fission catalyzed by a... 

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 degradation of tryptophan by Pseudomonas fluorescens that takes place via the [1-ketoadipate pathway and by P. acidovorans that utilizes the quinoline pathway (Stanier 1968) ... 

A formally comparable pathway is used by a strain of Alcaligenes sp. that degrades 4-hydroxyacetophenone via 4-hydroxybenzoyl methanol to 4-hydroxybenzoate this is further metabolized to P ketoadipate via 3,4-dihydroxybenzoate (Figure 6.32b) (Flopper et... 

Figure 8.4 Biosynthetic potentiai of Pseudomonas putida. Extended carbon core metabolism of Pseudomonas putida KT2440 including the major catabolic routes of Entner-Doudoroff pathway, Embden-Meyerhof-Parnas pathway, pentose phosphate pathway, tricarboxylic acid cycle, glyoxylate shunt, anaplerotic reactions, fatty acid de novo biosynthesis, p-oxidation of fatty acids, as well as the convergent -ketoadipate pathway for catabolism of aromatics. Known pathways for respective precursor supply for the broad product spectrum of P. putida KT2440 are indicated by light red arrows. Natural products and substrates are highlighted in black, heterologous products and substrates In red.

Figure 3.9. Bacterial degradation of benzoate and p-hydroxybenzoate by the -ketoadipate pathway...

The mechanism for the hydroxylation of aromatic substrates by flavoprotein monooxygenases has been the subject of signiflcant research interest and controversy over the past decade. These enzymes (p-hydroxybenzoate hydroxylase, phenol hydroxylase, and melilotate hydroxylase) catalyze the initial step in the )8-ketoadipic acid pathway, the hydroxylation of substituted phenols into catechols (Scheme 55). Oxygen is required as cosubstrate, which is activated by the reduced FAD cofactor. The complex mechanism for the oxidative half-reaction is thought to consist of at least four steps and three intermediates 239-242) and to involve a controversial 4a,5-ring-opened flavin 242, 249, 250) (Scheme 56). The flavin C4a-hydroperoxy intermediate 64 and flavin C4a-hydroxy intermediate 65 have been assigned the structures shown in Scheme 56 based on the UV absorbance spectra of various model compounds compared with that of the modified enzyme cofactor alkylated at N(5) 243). However, evidence for the intermediacy of various ring-opened flavin species has been tentative at best, as model compounds and model reactions do not support such an intermediate 242). 

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