Tryptophan halogenase

Keller S, T Wage, K Hohaus, M Holzer, E Eichjorn, K-H van Pee (2000) Purification and partial characterization of tryptophan 7-halogenase (PrnA) from Pseudomonas fluorescens. Angew Chem Int Ed 39 2300-2302. 

Dong, C., Flecks, S., Unversucht, S. et al. (2005) Tryptophan 7-halogenase (PrnA) structure suggests a mechanism for regioselective chlorination. Science, 309, 2216-2219. 

FADH2 halogenases such as tryptophan 7-halogenase have been shown to catalyze regioselective halogenation of a wide range of indole derivatives and aromatic heterocycles, where a cofactor regeneration system has recently been developed to use only a catalytic amount of cofactors (Scheme 7.13) [52, 53]. 

R2 = amine, alkyl, nitrile Scheme 7.13 Halogenation of indoles by tryptophan 7-halogenase. 

Scheme 7.14 Tryptophan 7-halogenases to create novel indolocarbazoles.

Fig. 4.2 A ribbon diagram of tryptophan 7-halogenase, an enzyme important in the biosynthesis of pyrrolnitrin and rebeccamycin. (Photo K.-H. van Pee and J. H. Naismith)...

Hdlzer M, Burd W, Reissig H-U, van Pee K-H (2001) Substrate Specificity and Regio-selectivity of Tryptophan 7-Halogenase from Pseudomonas fluorescens BL915. Adv Synth Catal 343 591... 

Dong C, Kotzsch A, Dorward M, van Pee K-H, Naismith JH (2004) Crystallization and X-ray Diffraction of a Halogenating Enzyme, Tryptophan 7-Halogenase, from Pseudomonas fluorescens. Acta Cryst D60 1438... 

Keller S, Wage T, Hohaus K, Holzer M, Eichhom E, van Pee K-H (2000) Purification and Partial Characterization of Tryptophan 7-Halogenase (PmA) from Pseudomonas fluores-cens. Angew Chem Int Ed 39 2300... 

Unversucht S, Hollmann F, Schmid A, van Pee K-H (2005) FADH2-Dependence of Tryptophan 7-Halogenase. Adv Synth Catal 347 1163... 

Figure 16.9-2. Hypothetical reaction mechanism of FADH2-dependent tryptophan 7-halogenase as an example of FADH2-dependent halogenases1201.

Figure 16.9-3. Substrates accepted by tryptophan 7-halogenase (a) indole derivatives, (b) phenylpyrrole derivatives the positions of chlorination are indicated by arrows 431.

The recently detected FADH2-dependent halogenases are substrate specific. Tryptophan 7-halogenase catalyzes the chlorination and bromination of d- and L-trypto-phan to 7-chloro- or 7-bromotryptophan, respectively1201. This enzyme also accepts a number of other indole derivatives such as tryptamine, indole-3-acetonitrile, 3-me-thylindole and 5-methylindole as substrates (Fig. 16.9-3a) 43L In addition to indoles, aminophenylpyrrole derivatives are also chlorinated by tryptophan 7-halogenase (Fig. 16.9-3b) 43L... 

Tryptophan 7-halogenase pyrrolnitrin-producing indole derivatives (Cl-, Br-) 20, 43... 

Figure 1.59 Formation of hypochlorous acid from FAD-4o -OOH (a) mechanism of tryptophan chlorination (b) catalyzed by tryptophan 7-halogenase and (c) catalyzed by halogenating enzyme RebH.

Bitto E, Huang Y, Bingman CA, Singh S, Thorson JS, Phillips GN. The structure of fiavin-dependent tryptophan 7-halogenase RebH. Proteins 2008 70 289-293. 

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