Reengineering a Tryptophan Halogenase To Preferentially Chlorinate a Direct Alkaloid Precursor (Record no. 47641)

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control field 20250625153922.0
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Transcribing agency CICY
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Classification number (OCLC) (R) ; Classification number, CALL (RLIN) (NR) B-13441
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Title Reengineering a Tryptophan Halogenase To Preferentially Chlorinate a Direct Alkaloid Precursor
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Volume/sequential designation Journal of the American Chemical Society, 133, p.19346-19349, 2011
520 3# - SUMMARY, ETC.
Summary, etc. Installing 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
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Personal name Glenn, W.S.
700 12 - ADDED ENTRY--PERSONAL NAME
Personal name Nims, E.
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Personal name O'Connor, S.E.
856 40 - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="https://drive.google.com/file/d/19PxNJeIqbel5opp81bvUJV-CshlKtpCn/view?usp=drivesdk">https://drive.google.com/file/d/19PxNJeIqbel5opp81bvUJV-CshlKtpCn/view?usp=drivesdk</a>
Public note Para ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
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Source of classification or shelving scheme Clasificación local
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  Clasificación local     Ref1 CICY CICY Documento préstamo interbibliotecario 25.06.2025   B-13441 25.06.2025 25.06.2025 Documentos solicitados