Synthesis of mitomycin analogs catalyzed by coupling of laccase with lipase and the kinetic model

BACKGROUND Mitomycin C (MMC) is one of the most important members of the mitomycin family that have been widely used as a strong antineoplastic antibiotic for treating various tumors. In this study, enzymatic oxidation/amination reaction of 2-methyl-1,4-hydroquinone with n -butylamine was carried out to synthesize 2-methyl-3- n -butylaminoyl-1,4-benzoquinone mitomycin analogs. RESULTS A kinetic model was developed based on an ordered sequential mechanism for this cascade reaction system catalyzed by two enzymes, which revealed that the limiting step of the system was the laccase-mediated oxidation of 2-methyl-3- n -butylaminoyl-4-hydro-1-quinone and removing the limiting step resulted in a yield increase from 88.3% to 96.7%. CONCLUSION The developed kinetic model fitted the test data very well, indicating that the reactions catalyzed by coupling of laccase with lipase might follow the ordered sequential mechanism with product inhibition. Synthesis of mitomycin analogs catalyzed by coupling of laccase with lipase has great potential for practical application. © 2020 Society of Chemical Industry