Straightforward Regeneration of Reduced Flavin Adenine Dinucleotide Required for Enzymatic Tryptophan Halogenation
(2019) In ACS Catalysis 9(2). p.1389-1395- 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 (FADH 2 ) 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... (More)
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 (FADH 2 ) 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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- author
- Ismail, Mohamed LU ; Schroeder, Lea ; Frese, Marcel ; Kottke, Tilman ; Hollmann, Frank ; Paul, Caroline E. and Sewald, Norbert
- publishing date
- 2019-02-01
- type
- Contribution to journal
- publication status
- published
- keywords
- enzymatic cofactor regeneration, FADH, flavin-dependent halogenases, hydride transfer, NADH mimics, regioselective chlorination
- in
- ACS Catalysis
- volume
- 9
- issue
- 2
- pages
- 7 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- scopus:85061038204
- ISSN
- 2155-5435
- DOI
- 10.1021/acscatal.8b04500
- language
- English
- LU publication?
- no
- id
- 7f28c866-7de9-4a38-93c4-13fc2a738d39
- date added to LUP
- 2023-08-28 11:43:23
- date last changed
- 2023-08-29 13:28:58
@article{7f28c866-7de9-4a38-93c4-13fc2a738d39, abstract = {{<p> 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 (FADH <sub>2</sub> ) 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.</p>}}, author = {{Ismail, Mohamed and Schroeder, Lea and Frese, Marcel and Kottke, Tilman and Hollmann, Frank and Paul, Caroline E. and Sewald, Norbert}}, issn = {{2155-5435}}, keywords = {{enzymatic cofactor regeneration; FADH; flavin-dependent halogenases; hydride transfer; NADH mimics; regioselective chlorination}}, language = {{eng}}, month = {{02}}, number = {{2}}, pages = {{1389--1395}}, publisher = {{The American Chemical Society (ACS)}}, series = {{ACS Catalysis}}, title = {{Straightforward Regeneration of Reduced Flavin Adenine Dinucleotide Required for Enzymatic Tryptophan Halogenation}}, url = {{http://dx.doi.org/10.1021/acscatal.8b04500}}, doi = {{10.1021/acscatal.8b04500}}, volume = {{9}}, year = {{2019}}, }