Cyclohexylamine oxidase as a useful biocatalyst for the kinetic resolution and dereacemization of amines

LeischHannes,; GrosseStephan,; IwakiHiroaki,; HasegawaYoshie,; LauPeter, C K

doi:10.1139/v11-086

Cited by 30 publications

(15 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The catalytic activity of these mutants towards chiral primary amines was shown to be higher than that towards simple primary amines. Leisch and co‐workers successfully synthesized an R amine by deracemization using an S ‐stereoselective cyclohexylamine oxidase from Brevibacterium oxydans IH‐35A 2c,d. More recently, Kohler et al.…”

Section: Comparison Of the Activities Of The Pkdao Variants[a]mentioning

confidence: 99%

Tailoring D‐Amino Acid Oxidase from the Pig Kidney to R‐Stereoselective Amine Oxidase and its Use in the Deracemization of α‐Methylbenzylamine

2014

View full text Add to dashboard Cite

The deracemization of racemic amines to yield enantioenriched amines using S-stereoselective amine oxidases (AOx) has recently been attracting attention. However, Rstereoselective AOx that are suitable for deracemization have not yet been identified. An R-stereoselective AOx was now evolved from porcine kidney d-amino acid oxidase (pkDAO) and subsequently use for the deracemization of racemic amines. The engineered pkDAO, which was obtained by directed evolution, displayed a markedly changed substrate specificity towards R amines. The mutant enzyme exhibited a high preference towards the substrate a-methylbenzylamine and was used to synthesize the S amine through deracemization. The findings of this study indicate that further investigations on the structure-activity relationship of AOx are warranted and also provide a new method for biotransformations in organic synthesis.

show abstract

Section: Comparison Of the Activities Of The Pkdao Variants[a]mentioning

confidence: 99%

Tailoring D‐Amino Acid Oxidase from the Pig Kidney to R‐Stereoselective Amine Oxidase and its Use in the Deracemization of α‐Methylbenzylamine

2014

View full text Add to dashboard Cite

show abstract

“…The cyclohexylamine biodegradation pathway leads ultimately to adipate, and includes the enzyme cyclohexanone monooxygenase (CHMO), a Baeyer-Villiger monooxygenase of known structure [19], [20]. The catalytic performance of CHAO was recently investigated, revealing activity towards a range of amine substrates [21]. We compare the structure of CHAO to its closest known structural relatives, highlighting important similarities and differences.…”

Section: Introductionmentioning

confidence: 99%

Structural Analysis of a Novel Cyclohexylamine Oxidase from Brevibacterium oxydans IH-35A

et al. 2013

Self Cite

View full text Add to dashboard Cite

Cyclohexylamine oxidase (CHAO) is a flavoprotein first described in Brevibacterium oxydans strain IH-35A that carries out the initial step of the degradation of the industrial chemical cyclohexylamine to cyclohexanone. We have cloned and expressed in Escherichia coli the CHAO-encoding gene (chaA) from B. oxydans, purified CHAO and determined the structures of both the holoenzyme form of the enzyme and a product complex with cyclohexanone. CHAO is a 50 kDa monomer with a PHBH fold topology. It belongs to the flavin monooxygenase family of enzymes and exhibits high substrate specificity for alicyclic amines and sec-alkylamines. The overall structure is similar to that of other members of the flavin monooxygenase family, but lacks either of the C- or N-terminal extensions observed in these enzymes. Active site features of the flavin monooxygenase family are conserved in CHAO, including the characteristic aromatic cage. Differences in the orientations of residues of the CHAO aromatic cage result in a substrate-binding site that is more open than those of its structural relatives. Since CHAO has a buried hydrophobic active site with no obvious route for substrates and products, a random acceleration molecular dynamics simulation has been used to identify a potential egress route. The path identified includes an intermediate cavity and requires transient conformation changes in a shielding loop and a residue at the border of the substrate-binding cavity. These results provide a foundation for further studies with CHAO aimed at identifying features determining substrate specificity and for developing the biocatalytic potential of this enzyme.

show abstract

“…[109] In a later report, the same authors improved the performance of this biocatalyst by rational design. Five single-point mutants were prepared and tested in the same process, finding that the activity of some mutants was enhanced.…”

Section: Using An Amino Oxidase and A Non-selective Chemical Reducingmentioning

confidence: 95%

Why Leave a Job Half Done? Recent Progress in Enzymatic Deracemizations

Díaz‐Rodríguez¹,

Lavandera

Gotor³

2015

CGC

View full text Add to dashboard Cite

Abstract. In recent years the usefulness of enzymatic systems to obtain a single stereoisomerically pure compound starting from a racemate has been expanded. Moreover, current advances in protein engineering, molecular biology and modeling tools are the basis to improve the catalytic properties of enzymes to face novel synthetic challenges. Also, medium engineering and novel immobilization methods of (bio)catalysts are enhancing the productivity of biocatalytic processes making them suitable for being scalable. The development of multienzymatic protocols and the combination of enzymes with other catalysts are providing a wide range of synthetic possibilities that are expanding the scope of these transformations even at industrial scale. Herein we will describe an overview of recent (chemo)enzymatic deracemizations, focusing on the strategy employed (dynamic kinetic resolution, stereoinversion, cyclic deracemization or enantioconvergent process), the type of substrate (e.g., alcohols, amines, carboxylic acid derivatives or carbonylic compounds), and the biocatalyst(s) used.

show abstract

Cyclohexylamine oxidase as a useful biocatalyst for the kinetic resolution and dereacemization of amines

Cited by 30 publications

References 35 publications

Tailoring D‐Amino Acid Oxidase from the Pig Kidney to R‐Stereoselective Amine Oxidase and its Use in the Deracemization of α‐Methylbenzylamine

Tailoring D‐Amino Acid Oxidase from the Pig Kidney to R‐Stereoselective Amine Oxidase and its Use in the Deracemization of α‐Methylbenzylamine

Structural Analysis of a Novel Cyclohexylamine Oxidase from Brevibacterium oxydans IH-35A

Why Leave a Job Half Done? Recent Progress in Enzymatic Deracemizations

Contact Info

Product

Resources

About