Dramatic Enhancement of Enantioselectivity of Biotransformations of β-Hydroxy Nitriles Using a Simple <i>O</i>-Benzyl Protection/Docking Group

Ma, Da‐You; Zheng, Qiang; Wang, De‐Xian; Wang, Mei‐Xiang

doi:10.1021/ol0610688

Cited by 29 publications

(15 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies of biotransformations using R. erythropolis AJ270 whole cells have indicated that the nitrile-degrading enzymes in the cells have high enantioselectivity [24,35,42,44]. In this two-enzyme system, enantioselectivity is largely due to the amidase because nitrile hydratase shows very low enantioselectivity with some substrates [43].…”

Section: R-(+)-2(c-f) (+/-)-1(c-f) S-(-)-3(c-f)mentioning

confidence: 99%

“…Two hundred microliters of isopropyl alcohol was added to resolve the precipitation after a process of ether extraction (700 ll) and blowdrying. Five microliters of the solution was used in the high-performance liquid chromatography (HPLC) assay as previously reported [23,24,44]. All products were characterized by their spectral data.…”

Section: Regio-and Stereoselectivity Of Amidasementioning

confidence: 99%

“…Substrate engineering, as an alternative method, seems to be useful in improving the efficiency and selectivity of biocatalysis. Ma et al [22][23][24] found that using the O-benzyl and N-benzyl protection/ docking method dramatically enhanced the enantioselectivity of biotransformations. The results of the current study indicate that, compared with free b-hydroxy and b-amino phenylpropionamides, the enzyme that catalyzed the hydrolysis of O-benzyl and N-benzyl phenylpropionamides afforded remarkably high enantioselective biotransformations.…”

Section: R-(+)-2(c-f) (+/-)-1(c-f) S-(-)-3(c-f)mentioning

confidence: 99%

“…The case of L-carnitine amidase is a rare example of stereoselectivity toward a b-substituted amide [15]. One study showed that under mild conditions, whole cells of R. erythropolis AJ270 transformed a-substituted racemic amides with high (S)-enantioselectivity into the corresponding enantiopure acids, but the enantiocontrol of the reaction was very disappointing when performed on racemic b-hydroxy and b-amino alkanenitriles [24].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Overexpression of a recombinant amidase in a complex auto-inducing culture: purification, biochemical characterization, and regio- and stereoselectivity

Xue

Chao

Wang

et al. 2011

J Ind Microbiol Biotechnol

View full text Add to dashboard Cite

Rhodococcus erythropolis AJ270 metabolizes a wide range of nitriles via the two-step nitrile hydratase/amidase pathway. In this study, an amidase gene from R. erythropolis AJ270 was cloned and expressed in Escherichia coli BL21 (DE3). The activity reached the highest level of 22.04 U/ml in a complex auto-inducing medium using a simplified process of fermentation operation. The recombinant amidase was purified to more than 95% from the crude lysate using Ni-NTA affinity chromatography and Superose S10-300 gel filtration. The V(max) and K(m) values of the purified enzyme with acetamide (50 mM) were 6.89 μmol/min/mg protein and 4.12 mM, respectively, which are similar to those of the enzyme from the wild-type cell. The enzyme converted racemic α-substituted amides, O-benzylated β-hydroxy amides, and N-benzylated β-amino amides to the corresponding (S)-acids with remarkably high enantioselectivity. The ionic liquid [BMIm][PF₆] (1-butyl-3-methylimidazolium hexafluorophosphate) enhanced the activity by 1.5-fold compared with water. The adequate expression of the enzyme and excellent enantioselectivity of the recombinant amidase to a broad spectrum of amides suggest that the enzyme has prospective industrial-scale practical applications in pharmaceutical chemistry.

show abstract

Section: R-(+)-2(c-f) (+/-)-1(c-f) S-(-)-3(c-f)mentioning

confidence: 99%

Section: Regio-and Stereoselectivity Of Amidasementioning

confidence: 99%

Section: R-(+)-2(c-f) (+/-)-1(c-f) S-(-)-3(c-f)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Overexpression of a recombinant amidase in a complex auto-inducing culture: purification, biochemical characterization, and regio- and stereoselectivity

Xue

Chao

Wang

et al. 2011

J Ind Microbiol Biotechnol

View full text Add to dashboard Cite

show abstract

“…The unprotected aliphatic, 3‐aminobutyronitrile 2 was obtained commercially and protected amino acid derivatives were prepared from this by employing standard protection protocols from literature as outlined in the supplementary information . The aromatic analogue 3‐amino‐3‐phenylpropionitrile 6 was prepared by adapting a procedure developed by Brady et al , to employ sodium triacetoxyborohydride in place of sodium cyanoborohydride for enamine reduction as .…”

Section: Resultsmentioning

confidence: 99%

Process Optimisation Studies and Aminonitrile Substrate Evaluation of Rhodococcus erythropolis SET1, A Nitrile Hydrolyzing Bacterium

et al. 2020

View full text Add to dashboard Cite

A comprehensive series of optimization studies including pH, solvent and temperature were completed on the nitrile hydrolyzing Rhodococcus erythropolis bacterium SET1 with the substrate 3-hydroxybutyronitrile. These identified temperature of 25°C and pH of 7 as the best conditions to retain enantioselectivity and activity. The effect of the addition of organic solvents to the biotransformation mixture was also determined. The results of the study suggested that SET1 is suitable for use in selected organo-aqueous media at specific ratios only. The functional group tolerance of the isolate with unprotected and protected β-aminonitriles, structural analogues of β-hydroxynitriles was also investigated with disappointingly poor isolated yields and selectivity obtained. The isolate was further evaluated with the αaminonitrile phenylglycinonitrile generating acid in excellent yield and ee (> 99 % (S) -isomer and 50 % yield). A series of pH studies with this substrate indicated pH 7 to be the optimum pH to avoid product and substrate degradation.

show abstract

Enantioselectivity of Enzymes

Hollmann

Otten

2009

Wiley Encyclopedia of Chemical Biology

View full text Add to dashboard Cite

The enantioselectivity of enzymes plays a central role within life and is manifold exploited by using biocatalysis as a key step in the development of fine chemicals and drug synthesis. Some of the most relevant examples are summarized in this article. Understanding the molecular background of this enantioselectivity is an ongoing topic in modern enzymology. Current approaches aiming at in‐depth comprehension comprise structure‐based molecular modeling as well as empirical methods. Based thereon, strategies to gain control over the enantioselectivity are developed including (semi‐)rational and purely random mutagenesis. In addition, reaction engineering approaches are discussed. In this respect, fast and robust methods to determine enzyme enantioselectivity are pivotal. Here, an overview of the current knowledge and the most exciting developments in the area of understanding, controlling, and exploiting enzyme enantioselectivity is given.

show abstract

Dramatic Enhancement of Enantioselectivity of Biotransformations of β-Hydroxy Nitriles Using a Simple O-Benzyl Protection/Docking Group

Cited by 29 publications

References 77 publications

Overexpression of a recombinant amidase in a complex auto-inducing culture: purification, biochemical characterization, and regio- and stereoselectivity

Overexpression of a recombinant amidase in a complex auto-inducing culture: purification, biochemical characterization, and regio- and stereoselectivity

Process Optimisation Studies and Aminonitrile Substrate Evaluation of Rhodococcus erythropolis SET1, A Nitrile Hydrolyzing Bacterium

Enantioselectivity of Enzymes

Contact Info

Product

Resources

About