Specific N-demethylation of verapamil by cytochrome P450 from Streptomyces griseus ATCC 13273.

ABSTRACT: Norverapamil, the N-demethylated derivative of verapamil, is a novel promising leading compound for attenuating multidrug resistance with less side effects compared with verapamil. However, the efficient synthetic method for norverapamil is absent. In this study, an innovative biotechnological method based on enzymatic catalysis was presented for the high-efficient production of norverapamil. CYP105D1, a cytochrome P450 from Streptomyces griseus ATCC 13273, was identified to carry out a one-step specific N-demethylation of verapamil along with putidaredoxin reductase (Pdr) and putidaredoxin (Pdx) as the redox partner. Docking calculations rationalized the specific N-demethylation observed in experiment and identified important amino acid residues for verapamil binding. Furthermore,

SUBMITTER: Shen C 

PROVIDER: S-EPMC6999465 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature