Table 2. HNL Productivity, Activity, and Enantiomeric Excess of Selected PlamHNL Variantsa.
variants | dAffinityb (kcal mol–1) | productivity (U L–1) | specific activityc (U mg–1) | % eefd |
---|---|---|---|---|
N85H | –0.9664 | 477 | 402 ± 36 | 85 |
L98W | –0.7173 | N.D. | N.D. | N.D. |
L98E | –0.6709 | N.D. | N.D. | N.D. |
N85Y | –0.6488 | 233 | 304 ± 18.2 | 92 |
R58W | –0.5245 | N.D. | N.D. | N.D. |
W109H | –0.4386 | 160 | 205 ± 14.2 | 22 |
A74W | –0.4163 | N.D. | N.D. | N.D. |
N85E | –0.3178 | 382 | 290 ± 7.6 | 53 |
R58K | –0.2335 | N.D. | N.D. | N.D. |
N85Q | –0.2192 | 180 | 165 ± 26.7 | 15 |
Y60A | –0.1977 | N.D. | N.D. | N.D. |
Y124A | –0.1061 | N.D. | N.D. | N.D. |
T95A | –0.0494 | 580 | 695 ± 42 | 86 |
N85H/T95A | 450 | 420 ± 8.6 | 81 | |
N85Y/T95A | 457 | 401 ± 8.5 | 88 | |
wild-type | 420 | 506 ± 7.8 | 76 |
All of variants were selected based on a calculation of the alanine or residue scanning functionality around 14 amino acid residues in the binding pocket using the MOE program to identify critical residues for affinity. N.D. = not detectable, which indicates the case that the measuring enzyme activity was the same as omitting the enzyme reaction (control).
dAffinity values refer to the relative binding affinity of the mutation to the wild-type protein. dAffinity is equal to the Boltzmann average of the relative affinities of the ensemble. A more negative value indicates a mutation with better affinity.
Specific activity was assayed after 5 min in a reaction mixture containing 2-chlorobenzaldehyde (50 mM) and KCN (100 mM) at 25 °C with the same amount (0.64 μg) of purified PlamHNL variants.
Enantiomeric excess was obtained for (R)-2-chloromandelonitrile synthesis by HPLC with the same concentration of purified PlamHNL variants (1.2 Unit).