scholarly journals Modulating the coupling efficiency of P450 BM3 by controlling water diffusion through access tunnel engineering

ChemSusChem ◽  
2021 ◽  
Author(s):  
Shuaiqi Meng ◽  
Yu Ji ◽  
Luo Liu ◽  
Mehdi D. Davari ◽  
Ulrich Schwaneberg
Keyword(s):  
Coupling Efficiency ◽  
Water Diffusion ◽  
Tunnel Engineering ◽  
P450 Bm3

scholarly journals Directed Evolution of P450 BM3 towards Functionalization of Aromatic O-Heterocycles

2019 ◽  
Vol 20 (13) ◽  
pp. 3353 ◽  
Author(s):  
Gustavo de Almeida Santos ◽  
Gaurao V. Dhoke ◽  
Mehdi D. Davari ◽  
Anna Joëlle Ruff ◽  
Ulrich Schwaneberg
Keyword(s):  
Directed Evolution ◽  
Bacillus Megaterium ◽  
Coupling Efficiency ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Building Blocks ◽  
Saturation Mutagenesis ◽  
P450 Monooxygenase ◽  
Initial Oxidation ◽  
P450 Bm3 ◽  
Total Turnover

The O-heterocycles, benzo-1,4-dioxane, phthalan, isochroman, 2,3-dihydrobenzofuran, benzofuran, and dibenzofuran are important building blocks with considerable medical application for the production of pharmaceuticals. Cytochrome P450 monooxygenase (P450) Bacillus megaterium 3 (BM3) wild type (WT) from Bacillus megaterium has low to no conversion of the six O-heterocycles. Screening of in-house libraries for active variants yielded P450 BM3 CM1 (R255P/P329H), which was subjected to directed evolution and site saturation mutagenesis of four positions. The latter led to the identification of position R255, which when introduced in the P450 BM3 WT, outperformed all other variants. The initial oxidation rate of nicotinamide adenine dinucleotide phosphate (NADPH) consumption increased ≈140-fold (WT: 8.3 ± 1.3 min−1; R255L: 1168 ± 163 min−1), total turnover number (TTN) increased ≈21-fold (WT: 40 ± 3; R255L: 860 ± 15), and coupling efficiency, ≈2.9-fold (WT: 8.8 ± 0.1%; R255L: 25.7 ± 1.0%). Computational analysis showed that substitution R255L (distant from the heme-cofactor) does not have the salt bridge formed with D217 in WT, which introduces flexibility into the I-helix and leads to a heme rearrangement allowing for efficient hydroxylation.

Coupling efficiency and sensitivity of an LED to a single-mode fibre

1986 ◽  
Vol 22 (21) ◽  
pp. 1110 ◽  
Author(s):  
D.N. Christodoulides ◽  
L.A. Reith ◽  
M.A. Saifi
Keyword(s):  
Coupling Efficiency ◽  
Single Mode ◽  
Single Mode Fibre ◽  
Mode Fibre

The Role of Protein Plasticity in Computational Rationalization Studies on Regioselectivity in Testosterone Hydroxylation by Cytochrome P450 BM3 Mutants

2012 ◽  
Vol 13 (2) ◽  
pp. 155-166 ◽  
Author(s):  
Stephanie B.A. de Beer ◽  
Laura A.H. van Bergen ◽  
Karlijn Keijzer ◽  
Vanina Rea ◽  
Harini Venkataraman ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
P450 Bm3 ◽  
Cytochrome P450 Bm3 ◽  
Testosterone Hydroxylation

Water Diffusion and Clustering on Pd(111)

Science ◽  
2002 ◽  
Vol 297 (5588) ◽  
pp. 1850-1852 ◽  
Author(s):  
T. Mitsui
Keyword(s):  
Water Diffusion

scholarly journals Engineering the biomimetic cofactors of NMNH for cytochrome P450 BM3 based on binding conformation refinement

RSC Advances ◽  
2021 ◽  
Vol 11 (20) ◽  
pp. 12036-12042
Author(s):  
Yao Liu ◽  
Yalong Cong ◽  
Chuanxi Zhang ◽  
Bohuan Fang ◽  
Yue Pan ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Rational Design ◽  
Design Strategy ◽  
Efficient Utilization ◽  
P450 Bm3 ◽  
Binding Conformation ◽  
Cytochrome P450 Bm3

A rational design strategy was proposed to improve the efficient utilization of alternative biomimetic cofactor by P450 BM3 enzyme.

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