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

Abstract

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

The aminoshikimic acid pathway in bacteria as source of precursors for the synthesis of antibacterial and antiviral compounds

“…Mitomycin C is the most important member of mitomycins, with a relevant anticancer activity. Mitomycin C is used to treat different cancers such as head and neck sarcoma, lung carcinoma, bladder cancer, hepatic carcinoma, esophageal carcinoma, pancreatic, and colorectal or anal cancer (Baindara & Mandal, 2020 ; Bass et al., 2013 ; Wolters et al., 2021 ; Zhang et al., 2020 ). Mitomycin C is a potent DNA cross-linking alkylating agent by two postulated alkylating centers.…”

“…The alkylation of DNA targets multiple guanine residues by reductive activation resulting in six covalent DNA adducts. DNA alkylation will block DNA synthesis, inhibiting cell proliferation, and several of the formed adducts are reported to induce cancer cell death (Wolters et al., 2021 ; Zhang et al., 2020 ). Mitomycin C possesses other relevant biological activities such as an antibiotic, antifibrotic, and immunosuppressive agent.…”

“…Mitomycin C possesses other relevant biological activities such as an antibiotic, antifibrotic, and immunosuppressive agent. However, severe adverse effects resulting from its high toxicity have limited its clinical application significantly (Zhang et al., 2020 ).…”

Asymmetric Sulfoxidation of Thioether Catalyzed by Soybean Pod Shell Peroxidase to Form Enantiopure Sulfoxide in Water‐in‐Oil Microemulsions: A Kinetic Model

“…There are many studies on the mechanism of the lipase‐catalyzed reaction, but a few on peroxidase. It is generally believed that many reactions catalyzed by enzymes obey one of the following two mechanisms: (1) Ping‐pong mechanism [23] and (2) Sequential mechanism [24–26] . The oxidation of sulfides catalyzed by peroxidase to enantiopure sulfoxides involves two intermediate forms of peroxidase: compounds I and II, which can actually be thought of as changing patterns of the peroxidase.…”

Laccase-catalyzed derivatization of 6-aminopenicillanic, 7-aminocephalosporanic and 7-aminodesacetoxycephalosporanic acid

“…The laccase-mediated reaction is a well-described method to synthesize novel antibiotics by enzymatic catalysis (Agematu et al 1993 ; Anyanwutaku et al 1994 ; Mikolasch et al 2016 ; Zhang et al 2020 ). These reactions enable the use of low-cost processes, mild reaction conditions-aqueous solvent systems, normal pressure, room temperature - to synthesize novel antibiotics.…”