• Journal of Microbiology and Biotechnology
• /
• 제34권3호
• /
• pp.725-734
• /
• 2024

CYP102A1 from Bacillus megaterium is an important enzyme in biotechnology, because engineered CYP102A1 enzymes can react with diverse substrates and produce human cytochrome P450-like metabolites. Therefore, CYP102A1 can be applied to drug metabolite production. Terpinen-4-ol is a cyclic monoterpene and the primary component of essential tea tree oil. Terpinen-4-ol was known for therapeutic effects, including antibacterial, antifungal, antiviral, and anti-inflammatory. Because terpenes are natural compounds, examining novel terpenes and investigating the therapeutic effects of terpenes represent responses to social demands for eco-friendly compounds. In this study, we investigated the catalytic activity of engineered CYP102A1 on terpinen-4-ol. Among CYP102A1 mutants tested here, the R47L/F81I/F87V/E143G/L188Q/N213S/E267V mutant showed the highest activity to terpinen-4-ol. Two major metabolites of terpinen-4-ol were generated by engineered CYP102A1. Characterization of major metabolites was confirmed by liquid chromatography-mass spectrometry (LC-MS), gas chromatography-MS, and nuclear magnetic resonance spectroscopy (NMR). Based on the LC-MS results, the difference in mass-to-charge ratio of an ion (m/z) between terpinen-4-ol and its major metabolites was 16. One major metabolite was defined as 1,4-dihydroxyp-menth-2-ene by NMR. Given these results, we speculate that another major metabolite is also a mono-hydroxylated product. Taken together, we suggest that CYP102A1 can be applied to make novel terpene derivatives.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.192.3-193
• /
• 2003

Aster species has been used in traditional chinese medicine for treatment of a bruies and asthma. On reviewing the literatures of this species, monoterpene glycosides, diterpenoids, triterpene glycosides, cyclic pentapeptides, oligopeptides and flavonoids 1) were isolated and some pharmacological activites were investigated 2). In continuation of our search for bioative components from Korean medicinal plants, we have examined Aster spathulifolius, collected from Jeju island on August 2001. (omitted)

• 약학회지
• /
• 제47권1호
• /
• pp.37-45
• /
• 2003

The present study was undertaken to investigate the anticancer activity of monoterepenes in the animal and the cancer cell line tests. Both of the noncyclic and cyclic monoterpenes showed significant life prolonging effects on ICR mouse with abdominal cancer induced by Sarcoma 180 cells up to 67.4％ and 63.5％ in case of linalool and geraniol, respectively. Linalool and geraniol also exhibited very excellent cytotoxicity against L1210 leukemic cells with $IC_{50}$/ value of 0.32 $\mu\textrm{g}$/mι in 5 days culture condition. In the presence of linalool and geraniol, the generation of $O_2$$^{[-10]}$ ion were found to be increased proportionally to the cytotoxicity arisen from these monoterpenes. Furthermore, the antioxidant enzymes activities such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) responsible for the conversion of $O_2$$^{[-10]}$ ion to $H_2O$$_2$ and then to $H_2O$ augmented remarkably by linalool and geraniol. All data put together it can be postulated that monoterpenes may kill abdominal cancer cells of ICR mouse probably by activating anticancer system of the body, whereas the death of L1210 cells may be due to the detrimental attacks of reactive oxygen species (ROS) including $O_2$$^{[-10]}$ in spite of antioxidant enzymes activities to overcome the ROS attacks.