Production of an O-desmethylated product, a major human metabolite, of rabeprazole sulfide by bacterial P450 enzymes

Cao, Ngoc Tan; Cha, Gun Su; Kim, Jeong-Hoon; Lee, Yujin; Yun, Chul-Ho; Nguyen, Ngoc Anh

doi:10.1016/j.enzmictec.2023.110328

Cited by 4 publications

(2 citation statements)

References 44 publications

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“…2 , Table S1 ). The mutants used in this study were obtained from previous studies [ 57 - 60 ]. The HPLC chromatogram of metabolites (M1 and M2) and terpinen-4-ol were eluted at retention times 7.2 min, 8 min, and 24.7 min, respectively.…”

Section: Resultsmentioning

confidence: 99%

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Production of Mono-Hydroxylated Derivatives of Terpinen-4-ol by Bacterial CYP102A1 Enzymes

Kim,

Park,

Jeong

et al. 2023

J. Microbiol. Biotechnol.

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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-dihydroxy- p -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.

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Section: Resultsmentioning

confidence: 99%

“…Mutants of the CYP102A1 gene were obtained from earlier work [ 57 - 60 ]. In this study, we selected M179 (R47L/F81I/F87V/E143G/L188Q/N213S/E267V) for bioconversion of 1,4-dihydroxy- p -menth-2-ene from terpinene-4-ol.…”

Section: Methodsmentioning

confidence: 99%

Production of Mono-Hydroxylated Derivatives of Terpinen-4-ol by Bacterial CYP102A1 Enzymes

Kim,

Park,

Jeong

et al. 2023

J. Microbiol. Biotechnol.

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Production of derivatives of α-terpineol by bacterial CYP102A1 enzymes

Kim,

Park,

Jeong

et al. 2024

Biotechnol Lett

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Biotransformation of selected secondary metabolites by Alternaria species and the pharmaceutical, food and agricultural application of biotransformation products

Tembeni,

Idowu,

Benrkia

et al. 2024

Nat. Prod. Bioprospect.

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Biotransformation is a process in which molecules are modified in the presence of a biocatalyst or enzymes, as well as the metabolic alterations that occur in organisms from exposure to the molecules. Microbial biotransformation is an important process in natural product drug discovery as novel compounds are biosynthesised. Additionally, biotransformation products offer compounds with improved efficacy, solubility, reduced cytotoxic and allows for the understanding of structure activity relationships. One of the driving forces for these impeccable findings are associated with the presence of cytochrome P450 monooxygenases that is present in all organisms such as mammals, bacteria, and fungi. Numerous fungal strains have been used and reported for their ability to biotransform different compounds. This review focused on studies using Alternaria species as biocatalysts in the biotransformation of natural product compounds. Alternaria species facilitates reactions that favour stereoselectivity, regioselectivity under mild conditions. Additionally, microbial biotransformation products, their application in food, pharmaceutical and agricultural sector is discussed in this review. Graphical Abstract

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Production of an O-desmethylated product, a major human metabolite, of rabeprazole sulfide by bacterial P450 enzymes

Cited by 4 publications

References 44 publications

Production of Mono-Hydroxylated Derivatives of Terpinen-4-ol by Bacterial CYP102A1 Enzymes

Production of Mono-Hydroxylated Derivatives of Terpinen-4-ol by Bacterial CYP102A1 Enzymes

Production of derivatives of α-terpineol by bacterial CYP102A1 enzymes

Biotransformation of selected secondary metabolites by Alternaria species and the pharmaceutical, food and agricultural application of biotransformation products

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