Straightforward Regeneration of Reduced Flavin Adenine Dinucleotide Required for Enzymatic Tryptophan Halogenation

Mohamed Ismail, Lea Schroeder, Marcel Frese, Tilman Kottke, Frank Hollmann, Caroline E. Paul, Norbert Sewald*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

Flavin-dependent halogenases are known to regioselectively introduce halide substituents into aromatic moieties, for example, the indole ring of tryptophan. The process requires halide salts and oxygen instead of molecular halogen in the chemical halogenation. However, the reduced cofactor flavin adenine dinucleotide (FADH2) has to be regenerated using a flavin reductase. Consequently, coupled biocatalytic steps are usually applied for cofactor regeneration. Nicotinamide adenine dinucleotide (NADH) mimics can be employed stoichiometrically to replace enzymatic cofactor regeneration in biocatalytic halogenation. Chlorination of l-tryptophan is successfully performed using such NADH mimics. The efficiency of this approach has been compared to the previously established enzymatic regeneration system using the two auxiliary enzymes flavin reductase (PrnF) and alcohol dehydrogenase (ADH). The reaction rates of some of the tested mimics were found to exceed that of the enzymatic system. Continuous enzymatic halogenation reaction for reaction scale-up is also possible.

Original languageEnglish
Pages (from-to)1389-1395
Number of pages7
JournalACS Catalysis
Volume9
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019

Fingerprint

Halogenation
Flavin-Adenine Dinucleotide
Tryptophan
NAD
Oxidoreductases
Halogens
Alcohol Dehydrogenase
Chlorination
Reaction rates
Alcohols
Enzymes
Salts
Oxygen
4,6-dinitro-o-cresol

Keywords

  • enzymatic cofactor regeneration
  • FADH
  • flavin-dependent halogenases
  • hydride transfer
  • NADH mimics
  • regioselective chlorination

Cite this

Ismail, M., Schroeder, L., Frese, M., Kottke, T., Hollmann, F., Paul, C. E., & Sewald, N. (2019). Straightforward Regeneration of Reduced Flavin Adenine Dinucleotide Required for Enzymatic Tryptophan Halogenation. ACS Catalysis, 9(2), 1389-1395. https://doi.org/10.1021/acscatal.8b04500
Ismail, Mohamed ; Schroeder, Lea ; Frese, Marcel ; Kottke, Tilman ; Hollmann, Frank ; Paul, Caroline E. ; Sewald, Norbert. / Straightforward Regeneration of Reduced Flavin Adenine Dinucleotide Required for Enzymatic Tryptophan Halogenation. In: ACS Catalysis. 2019 ; Vol. 9, No. 2. pp. 1389-1395.
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abstract = "Flavin-dependent halogenases are known to regioselectively introduce halide substituents into aromatic moieties, for example, the indole ring of tryptophan. The process requires halide salts and oxygen instead of molecular halogen in the chemical halogenation. However, the reduced cofactor flavin adenine dinucleotide (FADH2) has to be regenerated using a flavin reductase. Consequently, coupled biocatalytic steps are usually applied for cofactor regeneration. Nicotinamide adenine dinucleotide (NADH) mimics can be employed stoichiometrically to replace enzymatic cofactor regeneration in biocatalytic halogenation. Chlorination of l-tryptophan is successfully performed using such NADH mimics. The efficiency of this approach has been compared to the previously established enzymatic regeneration system using the two auxiliary enzymes flavin reductase (PrnF) and alcohol dehydrogenase (ADH). The reaction rates of some of the tested mimics were found to exceed that of the enzymatic system. Continuous enzymatic halogenation reaction for reaction scale-up is also possible.",
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Ismail, M, Schroeder, L, Frese, M, Kottke, T, Hollmann, F, Paul, CE & Sewald, N 2019, 'Straightforward Regeneration of Reduced Flavin Adenine Dinucleotide Required for Enzymatic Tryptophan Halogenation', ACS Catalysis, vol. 9, no. 2, pp. 1389-1395. https://doi.org/10.1021/acscatal.8b04500

Straightforward Regeneration of Reduced Flavin Adenine Dinucleotide Required for Enzymatic Tryptophan Halogenation. / Ismail, Mohamed; Schroeder, Lea; Frese, Marcel; Kottke, Tilman; Hollmann, Frank; Paul, Caroline E.; Sewald, Norbert.

In: ACS Catalysis, Vol. 9, No. 2, 01.02.2019, p. 1389-1395.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Straightforward Regeneration of Reduced Flavin Adenine Dinucleotide Required for Enzymatic Tryptophan Halogenation

AU - Ismail, Mohamed

AU - Schroeder, Lea

AU - Frese, Marcel

AU - Kottke, Tilman

AU - Hollmann, Frank

AU - Paul, Caroline E.

AU - Sewald, Norbert

PY - 2019/2/1

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N2 - Flavin-dependent halogenases are known to regioselectively introduce halide substituents into aromatic moieties, for example, the indole ring of tryptophan. The process requires halide salts and oxygen instead of molecular halogen in the chemical halogenation. However, the reduced cofactor flavin adenine dinucleotide (FADH2) has to be regenerated using a flavin reductase. Consequently, coupled biocatalytic steps are usually applied for cofactor regeneration. Nicotinamide adenine dinucleotide (NADH) mimics can be employed stoichiometrically to replace enzymatic cofactor regeneration in biocatalytic halogenation. Chlorination of l-tryptophan is successfully performed using such NADH mimics. The efficiency of this approach has been compared to the previously established enzymatic regeneration system using the two auxiliary enzymes flavin reductase (PrnF) and alcohol dehydrogenase (ADH). The reaction rates of some of the tested mimics were found to exceed that of the enzymatic system. Continuous enzymatic halogenation reaction for reaction scale-up is also possible.

AB - Flavin-dependent halogenases are known to regioselectively introduce halide substituents into aromatic moieties, for example, the indole ring of tryptophan. The process requires halide salts and oxygen instead of molecular halogen in the chemical halogenation. However, the reduced cofactor flavin adenine dinucleotide (FADH2) has to be regenerated using a flavin reductase. Consequently, coupled biocatalytic steps are usually applied for cofactor regeneration. Nicotinamide adenine dinucleotide (NADH) mimics can be employed stoichiometrically to replace enzymatic cofactor regeneration in biocatalytic halogenation. Chlorination of l-tryptophan is successfully performed using such NADH mimics. The efficiency of this approach has been compared to the previously established enzymatic regeneration system using the two auxiliary enzymes flavin reductase (PrnF) and alcohol dehydrogenase (ADH). The reaction rates of some of the tested mimics were found to exceed that of the enzymatic system. Continuous enzymatic halogenation reaction for reaction scale-up is also possible.

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