Zwitterionic peptides encircling-assisted enhanced catalytic performance of lysine decarboxylase for cadaverine biotransformation and mechanism analyses

Abstract

Inducible lysine decarboxylase (CadA) is the core enzyme in biosynthesis of 1,5-diaminopentane (cadaverine, DAP) which is an important raw material of bio-polyamide. To improve the activity and stability of CadA, EKylation strategy was employed. In detail, the C-terminus of CadA monomer was engineered with an alternating peptide of lysine (Lys, K) and glutamate (Glu, E). This peptide was a natural analogue of zwitterionic polymer, resulting in CadA decamer with 10 tails surrounding and enzyme microenvironments changing. As a result, the enzymatic activity of engineered CadA (CadA-EK) was doubled than that of wild-type CadA and the stability of CadA-EK was enhanced substantially. Besides, molecular docking and dynamic simulation were adopted to elucidate the enhancement of enzymatic properties. Finally, a “Hug-Handshake” model was proposed to explain the catalytic performance improvement of CadA-EK. These results pave the way for developing high-efficiency biocatalyst in synthesis of cadaverine.