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

Ismail, Mohamed LU orcid ; Schroeder, Lea ; Frese, Marcel ; Kottke, Tilman ; Hollmann, Frank ; Paul, Caroline E. and Sewald, Norbert (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
; ; ; ; ; and
publishing date
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}},
}