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Personendaten zu Christian Schnepel

  Christian Schnepel
Christian Schnepel
PhD Student
Raum: F2-225
Telefon: 0521 106 67090
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Engineering of flavin-dependent tryptophan-halogenases


Halogenated compounds play a major role in synthetic chemistry. They allow to build up organic scaffolds and serve as starting material in fundamental organic transformations like Pd-catalyzed cross couplings and nucleophilic substitutions. Therefore, haloarenes are important building blocks in the synthetic route towards valuable chemicals, agrochemicals and pharmaceuticals.

Conventional methods of halogenation require harsh reaction conditions and lack selectivity. Often mixtures of different isomers are obtained that result in a low overall yield of the desired product. Enzymatic halogenation is considered a promising, sustainable alternative. As halogen substituents are a widespread motif in natural products, different types of halogenating enzymes evolved in nature. The FADH2-dependent tryptophan-halogenase RebH from the actinomycete Lechevalieria aerocolonigenes catalyzes the regioselective incorporation of a halogen substituent at the C7 position of the indole moiety under ambient conditions. Molecular oxygen and non-toxic halide salts like NaCl or NaBr are required and the reaction proceeds at room temperature at a nearly neutral pH value.[1-2]

Recently, the synthetic purpose of tryptophan-halogenases has been investigated. The heterologous expression of RebH in E. coli and the following regioselective halogenation of tryptophan and some related derivatives could be demonstrated using purified or immobilized enzyme, respectively.[3-5]

A major drawback of enzymatic halogenation is the low catalytic activity of halogenases in combination with its limited substrate scope. Protein engineering seems as a powerful tool to further expand the application potential of tryptophan-halogenases. Random-based mutations are introduced and the resulting halogenase variants are screened for the desired properties, e. g. improved stability or altered substrate selectivity. In a stepwise high-throughput approach novel halogenase variants result that might be utilized in organic synthesis.


References

[1] E. Yeh, S. Garneau, C. T. Walsh, Proc. Natl. Acad. Sci. U. S. A.2005, 102, 3960 - 3965.
[2] E. Bitto, Y. Huang, C. A. Bingman, S. Singh, J. S. Thorson, G. N. Phillips, Proteins2008,

70, 289 - 293.
[3] J. T. Payne, M. C. Andorfer, J. C. Lewis, Angew. Chem. Int. Ed. 2013, 52, 5271 - 5274.
[4] M. Frese, P. H. Guzowska, H. Voß, N. Sewald, ChemCatChem 2014, 6, 1270 - 1276.
[5] M. Frese, N. Sewald, Angew. Chem. Int. Ed.2014, in press (DOI

10.1002/anie.201408561R1)


Personendaten

Sie finden hier Kontaktdaten und Informationen zu den Arbeitsbereichen der Mitarbeiter des Arbeitskreises Organische Chemie III.

Sekretariat

Fr. Iris Dopheide
Raum:F2-139
Telefon:0521 106 6963
Fax:0521 106 8094
E-Mail:sekretariat.oc3@uni-bielefeld.de