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These results underline the importance of the Ca2+ binding sites predicted in these outer regions for stability and activity of pernisine. KEY POINTS • Aggregation of produced pernisine was prevented by translocation into periplasm. • Thermostability of mature pernisine was increased. • The outer regions of the catalytic core are required for pernisine thermostability. Angiogenesis is closely related to the pathophysiology of diseases such as cancer or ischemia. Here, we investigated the effect of lidocaine at clinically effective blood c