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245	1	0	_aReengineering a Tryptophan Halogenase To Preferentially Chlorinate a Direct Alkaloid Precursor
490	0		_vJournal of the American Chemical Society, 133, p.19346-19349, 2011
520	3		_aInstalling halogens onto natural products can generate compounds with novel or improved properties. Notably, enzymatic halogenation is now possible as a result of the discovery of several classes of halogenases; however, applications are limited because of the narrow substrate specificity of these enzymes. Here we demonstrate that the flavin-dependent halogenase RebH can be engineered to install chlorine preferentially onto tryptamine rather than the native substrate tryptophan. Tryptamine is a direct precursor to many alkaloid natural products, including approximately 3000 monoterpene indole alkaloids. To validate the function of this engineered enzyme in vivo, we transformed the tryptamine-specific RebH mutant (Y455W)into the alkaloid-producing plant Madagascar periwinkle (Catharanthus roseus)and observed the de novo production of the halogenated alkaloid 12-chloro-19, 20-dihydroakuammicine. While wild-type (WT)RebH has been integrated into periwinkle metabolism reviously, the resulting tissue cultures accumulated substantial levels of 7-chlorotryptophan. Tryptophan decarboxylase, the enzyme that converts tryptophan to tryptamine, accepts 7-chlorotryptophan at only 3
700	1	2	_aGlenn, W.S.
700	1	2	_aNims, E.
700	1	2	_aO'Connor, S.E.
856	4	0	_uhttps://drive.google.com/file/d/19PxNJeIqbel5opp81bvUJV-CshlKtpCn/view?usp=drivesdk _zPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
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