A-Keto acid-dependent enzymes

Other examples of a-keto acid-dependent enzymes are mammalian proline hydroxylase and bacterial clavaminate synthase [113]. The latter enzyme is of particular interest as it is responsible for the catalysis of three individual steps in the biosynthesis of the (3-lactamase inhibitor clavulanic acid (Scheme 10.30). 

Other non-heme enzymes that use dioxygen are 4-methoxy-benzoate O-demethylase, extradiol catechol dioxygenases, the oxidoreductase isopenicillin N synthase, and a-keto acid-dependent enzymes (28). Moreover, the BH4-dependent glyceryl-ether monooxygenase (GEM) also appears to be dependent on nonheme iron for catalysis (see also Section I.E). 

The a-keto acid-dependent enzymes [206-208] catalyze a diverse array of reactions (Figure 26) involving functionalization of an unactivated C—H bond concomitant with the oxidative decarboxylation of a keto acid. For the hydroxylation... 

Figure 26 Some reactions catalyzed by a-keto acid-dependent enzymes.

Despite the limited information about the coordination environment of the metal center, a mechanism for the a-keto acid-dependent enzymes has been proposed (Figure 27) [222] in which the a-keto acid binds to the iron center and primes it for 02 binding. Attack of the bound 02 on the coordinated a-keto acid at the C-2 position results in decarboxylation of the a-keto acid to give an Fe(II)-peroxy derivative that can react with substrate either directly or via a high-valent iron-oxo intermediate to give the oxygenated substrate, a carboxylic acid, and the starting Fe(II) enzyme. 

Figure 11 Crystal structures of stages in the catalytic cycle of a-keto acid-dependent enzymes (a) the binary complex of CarC (lNX4.pdb), (b) the ternary complex of TauD (IGQW.pdb), and (c) the NO adduct of the ternary complex of CAS (IGVG.pdb)...

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