Haloalkane dehydrogenase

The haloalkane dehydrogenase is believed to act by using one of its side chain carboxylates to dis place chloride by an Sn2 mechanism (Recall the reac tion of carboxylate ions with alkyl halides from Table 8 1 )... 

Substitution reactions on aliphatic compounds are some of the most prevalent reactions known. Nature needs to perform these reactions, too, but at a rate appropriate for metabolism. Hence, enzymes are involved for many such reactions. As one example, the enzyme haloalkane dehydrogenase from the bacteria Xanthobacter autotrophicus catalyzes the detoxification of 1,2-dichloroethane. Many of the methods of catalysis noted in Chapter 9 are operative with this enzyme, such as proximity of the nucleophile and stabilization of the transition state. 

Amino acid sequence relationships have suggested a number of HYL families based on percent identity, enzymes with >40% identity belonging to the same family [48]. Families so identified include the mammalian microsomal EH (HYL1), the mammalian cytosolic EH (HYL2), the plant cytosolic EH (HYL3), and bacterial C-X bond hydrolases (haloacid dehydrogenases, HAD, and haloalkane dehalogenases, HLD). 

Another reaction of dehalogenation, the oxidative dehalogenation of haloalkyl groups, summarized in Fig. 11.3,b (Chapt. 8 in [50]), has also been observed in mammals and other organisms. Here, the haloalkane is oxidized by a cytochrome P450 enzyme to form a hydroxylated intermediate that loses HX to become a carbonyl derivative. The latter is then reduced by dehydrogenases to the corresponding alcohol (Fig. 11.3,c), or, when the carbonyl derivative is an aldehyde, oxidation to the acid can occur (Fig. 11.3,c). 

Some examples of emerging enzyme classes that are rapidly making an impact in synthetic organic chemistry are shown in Figure 16.4 alcohol dehydrogenase for the reduction of ketones [30], transaminase [31], and haloalkane dehalogenase... 

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