Bacterial Degradation of Quinoline and Derivatives—Pathways and Their Biocatalysts

Abstract

A series of interesting enzymes were discovered during investigations on the degradation of quinoline by microorganisms. These include the molybdenum-containing hydroxylases that catalyze the transformation 1→2 and the unusual 2,4-dioxygenases that catalyze the reaction 3→4. The application of the hydroxylases may even be interesting in industry, because several quinoline derivatives are used as pharmaceuticals or agrochemicals.

Regioselective aromatic hydroxylation of quinaldine by water using quinaldine 4-oxidase in recombinant Pseudomonas putida

“…Considering the application point of view, the ability of Qox to catalyze carbon oxyfunctionalization with low requirements for molecular oxygen makes it a very interesting enzyme for industrial oxyfunctionalization processes. The class of pterin-dependent hydroxylating dehydrogenases comprises a broad range of industrially interesting enzymes for the hydroxylation of highly activated carbon (e.g., xanthine, nicotine-, 6-hydroxynicotinate-, isonicotinate-, and nicotinate dehydrogenases), moderately activated heteroaromatic ring carbon (e.g., Qox, quinoline 2-, isoquinoline 1-, quinoline 4-carboxylate 2-, and quinaldic acid 4-oxidoreductases), and even rather unactivated benzylic carbon (e.g., ethylbenzene dehydrogenase) [5,15]. Together with the high process efficiency achieved in this study (with Qox) and by Lonza (with nicotinate dehydrogenase), this emphasizes the broad scope of these water incorporating enzymes.…”

“…In addition, the necessity for the regeneration of redox cofactors such as NADH or NADPH leads to increased costs and complexity, independent of the biocatalyst form used, i.e., whole cells or isolated enzymes [57]. In contrast to oxygenases, Mo-containing dehydrogenases use water as oxygen donor and produce reducing equivalents during hydroxylation [15,21]. Thus, these enzymes have the potential to overcome the limitations encountered with other oxidoreductases, e.g., oxygen supply, reactive oxygen species, and cofactor regeneration, for efficient in vivo oxyfunctionalization reactions.…”

“…Remarkably, quinoline, 8-chloroquinaldine, 2-and 8-monochloroquinoline, isoquinoline, 1,2-benzodiazine, quinazoline, and phthalazine are converted at a higher rate than quinaldine, the prototype substrate serving as model substrate in this study. Furthermore, Qox oxidizes aromatic aldehydes such as benzaldehyde, salicylaldehyde, vanillin, and cinnamaldehyde to the corresponding acids [15,50]. Short-chain aliphatic aldehydes are, however, not converted.…”

Mechanistic aspects of molybdenum-containing enzymes

“…In some of these the molybdenum-bound H P O (or OH group) is transferred as a nucleophile; in others the oxygen is transferred from an MoNO species as an electrophile and, again in others, ¢rst a molybdenum-carbon bond is formed with the substrate, followed by addition of molybdenum-coordinated water. Experimental details in favor of or against these mechanisms have been discussed in recent reviews [1,28].…”

The structural use of carbostyril in physiologically active substances

“…5). 17 Biologically, this implied that the amide bond of carbostyril, which is different from the external amide bonds of some other compounds, was not enzymatically cleaved. Furthermore, this internal amide is relatively tolerant to chemical alkaline hydrolysis.…”