A new mechanism of enantioselectivity toward chiral primary alcohol by lipase from Pseudomonas cepacia

Xiao, Meng; Guo, Li; Xu, Gang; Wu, Jianping; Yang, Lirong

doi:10.1016/j.molcatb.2014.08.014

Cited by 10 publications

(4 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the electronic effect-guided mutants, the distance between polar OH or SH groups and N atom of pyridyl made a major contribution to the stereoselectivity improvement theoretically. [14] According to the X-ray structure of CALB, the 104 site located in the bottom of the stereospecificity pocket, resulting in a shorter distance and stronger intermolecular force between the 104 polar residues and N atom of pyridin-4-yl (1 a) than those of pyridin-3-yl (1 b) and pyridin-2-yl (1 c). Therefore, the best KR enantioselectivity of 1 a (E > 200, entries 2 and 4 in Table S4) catalyzed by CALB mutants was higher than 1 b (E = 5, entry 11 in Table S4) and 1 c (E = 44, entry 21 in Table S4).…”

Section: Communicationsmentioning

confidence: 99%

Electronic Effect‐Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols

Lou

et al. 2021

Adv Synth Catal

View full text Add to dashboard Cite

Herein, we developed an electronic effect-guided rational design strategy to enhance the enantioselectivity of Candida antarctica lipase B (CALB) mutants towards bulky pyridyl(phenyl) methanols. Compared to W104A mutant previously reported with reversed S-stereoselectivity toward sec-alcohols, three mutants (W104C, W104S and W104T) displayed significant improvement of Senantioselectivity in the kinetic resolution (KR) of various phenyl pyridyl methyl acetates due to the increased electronic effects between pyridyl and polar residues. The electronic effects were also observed when mutating other residues surrounding the stereospecificity pocket of CALB, such as T42A, S47A, A281S or A281C, and can be used to manipulate the stereoselectivity. A series of bulky pyridyl(phenyl) methanols, including S-(4-chlorophenyl)(pyridin-2-yl) methanol (S-CPMA), the intermediate of bepotastine, were obtained in good yields and ee values.

show abstract

Section: Communicationsmentioning

confidence: 99%

Electronic Effect‐Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols

Lou

et al. 2021

Adv Synth Catal

View full text Add to dashboard Cite

show abstract

“…Chiral alcohols are widely used in organic synthesis, especially as building blocks in the preparation of chiral pharmaceutical compounds, such as L-chlorprenaline, (S)-fluoxetine and (R)-denopamine. [8][9][10] Therefore, cells can be used as a source of enzymes for the production of chiral alcohols, mainly via ketone reduction. The enzymes responsible for catalyzing the reaction are cofactor-dependent keto-reductases or alcohol dehydrogenases.…”

Section: Chiral Alcoholsmentioning

confidence: 99%

Production of chiral compounds using immobilized cells as a source of biocatalysts

Kisukuri

Andrade

2015

Org. Biomol. Chem.

View full text Add to dashboard Cite

The importance of chiral compounds in all fields of technology and life sciences is shown. Small chiral molecules are mainly used as building blocks in the synthesis of more complex and functionalized compounds. Nature creates and imposes stereoselectivity by means of enzymes, which are highly efficient biocatalysts. The use of whole cells as a biocatalyst source is a promising strategy for avoiding some drawbacks associated with the use of pure enzymes, especially their high cost. The use of free cells is also challenging, since cell lysis can also occur under the reaction conditions. However, cell immobilization has been employed to increase the catalytic potential of enzymes by extending their lifetimes in organic solvents and non-natural environments. Besides, immobilized cells maintain their biocatalytic performance for several reaction cycles. Considering the above-mentioned arguments, several authors have synthesized different classes of chiral compounds such as alcohols, amines, carboxylic acids, amides, sulfides and lactones by means of immobilized cells. Our aim was to discuss the main aspects of the production of chiral compounds using immobilized cells as a source of biocatalysts, except under fermentation conditions.

show abstract

“…Esters of secondary alcohols were synthesized from their corresponding alcohol in our lab following the procedure given. 25 Alcohol and triethylamine (molar ratio = 1 : 1.5) were mixed in an ice bath. Acyl chloride was slowly added next.…”

Section: Synthesis Of Substratesmentioning

confidence: 99%

“…Chemical modification on the lipase and molecular dynamics simulations indicated that Tyr 29 located within the catalytic cavity affected the enantioselectivity significantly via the hydrogen bond with the O non-α of the substrate. 25 In the present study, a combination of chemical modification, molecular dynamics simulation and MALDI-TOF-MS was employed to shed light on effects of chemical modification on the p-NPP catalytic activity and enantioselectivity towards secondary alcohols of PcL. Enantioselectivity catalyzed by modified PcL towards 5 pairs of different chiral secondary alcohol esters was improved by 2-to 4-fold and the catalytic activity of EDA-PcL increased by about 6-fold.…”

Section: Introductionmentioning

confidence: 99%

Enantioselectivity and catalysis improvements of Pseudomonas cepacia lipase with Tyr and Asp modification

Yue

et al. 2015

Catal. Sci. Technol.

View full text Add to dashboard Cite

A concise strategy to improve the p-NPP Ĳp-nitrophenyl palmitate) catalytic activity and enantioselectivity towards secondary alcohols of Pseudomonas cepacia lipase (PcL) has been described. The PcL was modified by I 3 − , N-acetyl imidazole (NAI), 1-Ĳ3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) and ethylenediamine (EDA) in the absence or presence of n-hexane, respectively. After being modified by the four modification reagents, the enantioselectivity (E value) of the PcL towards secondary alcohols was enhanced by 2-to 4-fold. The catalytic activity of EDA-PcL was increased by about 6-fold. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis of modified PcL showed that Tyr 4 , Tyr 29 , Tyr 45 , Tyr 95 , Asp 36 and Asp 55 were the modified sites. When Tyr 29 was modified, the E value of PcL towards secondary alcohols was largely improved. MALDI-TOF-MS characterization and molecular dynamics simulation of the lipase indicated that Tyr 29 located inside the catalytic cavity had a significant impact on the E value. The strong steric hindrance of acetyl and iodine ion to the groups on the chiral center of the substrates is responsible for the improvement. In addition, the enhancement of hydrophobicity on the surface of the lipase due to the sidechain replacement of Asp with uncharged hydrophobic groups also improved the E value.

show abstract

A new mechanism of enantioselectivity toward chiral primary alcohol by lipase from Pseudomonas cepacia

Cited by 10 publications

References 43 publications

Electronic Effect‐Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols

Electronic Effect‐Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols

Production of chiral compounds using immobilized cells as a source of biocatalysts

Enantioselectivity and catalysis improvements of Pseudomonas cepacia lipase with Tyr and Asp modification

Contact Info

Product

Resources

About