Protein engineering of carbonyl reductase for asymmetric synthesis of ticagrelor precursor (1S)-2-chloro-1-(3,4-difluorophenyl)ethanol

Weng, Chun-Yue; Gao, Xiao-Fan; Liu, Hua-Tao; Chu, Rong-Liang; Xie, Wei-Bang; Wang, Yajun; Zheng, Yu‐Guo

doi:10.1016/j.bej.2022.108600

Cited by 5 publications

(2 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nitrogen was used as a carrier gas at a split ratio of 30:1 ( v / v ). The column temperature was set at 160°C for 10 min, and injector and flame ionization detector temperatures were maintained at 250°C (Weng et al, 2022).…”

Section: Methodsmentioning

confidence: 99%

Computer‐directed rational design enhanced the thermostability of carbonyl reductase LsCR for the synthesis of ticagrelor precursor

Xu,

Chu,

Liu

et al. 2024

Biotech & Bioengineering

View full text Add to dashboard Cite

Carbonyl reductases are useful for producing optically active alcohols from their corresponding prochiral ketones. Herein, we applied a computer‐assisted strategy to increase the thermostability of a previously constructed carbonyl reductase, LsCRM4 (N101D/A117G/F147L/E145A), which showed an outstanding activity in the synthesis of the ticagrelor precursor (1S)‐2‐chloro‐1‐(3,4‐difluorophenyl)ethanol. The stability changes introduced by mutations at the flexible sites were predicted using the computational tools FoldX, I‐Mutant 3.0, and DeepDDG, which demonstrated that 12 virtually screened mutants could be thermally stable; 11 of these mutants exhibited increased thermostability. Then a superior mutant LsCRM4‐V99L/D150F was screened out from the library that was constructed by iteratively combining the beneficial sites, which showed a 78% increase in activity and a 17.4°C increase in melting temperature compared to LsCRM4. Our computer‐assisted design and combinatorial strategy dramatically increased the efficiency of thermostable enzyme production.

show abstract

Section: Methodsmentioning

confidence: 99%

Computer‐directed rational design enhanced the thermostability of carbonyl reductase LsCR for the synthesis of ticagrelor precursor

Xu,

Chu,

Liu

et al. 2024

Biotech & Bioengineering

View full text Add to dashboard Cite

show abstract

“…26–28 In fact, nicotinamide adenine dinucleotides, NADH and NADPH are indispensable cofactors involved in some redox bioreactions. 29,30 Glucose dehydrogenase (GDH) and formate dehydrogenase (FDH) are often utilized to regenerate co-factors through the consumption of the corresponding co-substrates in the manufacture of alcohols. 31,32 In an ideal bioreduction medium, both reductases and oxidases for cofactor regeneration should better come from the same kind of bacteria cells.…”

Section: Introductionmentioning

confidence: 99%

Significantly enhanced bioconversion of high titer biomass-derived furfural to furfuryl alcohol by robust endogenous aldehyde reductase in a sustainable way

Di,

Liao,

et al. 2023

Green Chem.

View full text Add to dashboard Cite

show abstract

Control of the activity and enantioselectivity in biocatalyzed procedures: immobilization, medium engineering, and protein engineering

Tang,

Alghiffary,

Matsuda

2024

Biocatalysis in Asymmetric Synthesis

View full text Add to dashboard Cite

Protein engineering of carbonyl reductase for asymmetric synthesis of ticagrelor precursor (1S)-2-chloro-1-(3,4-difluorophenyl)ethanol

Cited by 5 publications

References 33 publications

Computer‐directed rational design enhanced the thermostability of carbonyl reductase LsCR for the synthesis of ticagrelor precursor

Computer‐directed rational design enhanced the thermostability of carbonyl reductase LsCR for the synthesis of ticagrelor precursor

Significantly enhanced bioconversion of high titer biomass-derived furfural to furfuryl alcohol by robust endogenous aldehyde reductase in a sustainable way

Control of the activity and enantioselectivity in biocatalyzed procedures: immobilization, medium engineering, and protein engineering

Contact Info

Product

Resources

About