It should be noted here that Tian et al. do report a few active HheG mutants with amino acid exchanges at position Y18 of motif 1, which they obtained during protein engineering of this enzyme with the aim to improve enantioselectivity. In their case, however, only whole-cell reactions have been performed, while we have been working with isolated enzymes instead. Thus, it is possible that those HheG mutants exhibit even more reduced stability or yield much less soluble enzyme compared to wild-type HheG, which is why we could have lost them during enzyme isolation and/or purification in our study. At the same time, this would reinforce our assumption that position 18 in HheG impacts protein folding and stability.