Production of a major metabolite of niclosamide using bacterial cytochrome P450 enzymes.
Enzyme Microb Technol
; 165: 110210, 2023 Apr.
Article
in English
| MEDLINE | ID: covidwho-2229844
ABSTRACT
Niclosamide has been proposed as a possible candidate for a Covid-19 drug. However, the metabolites of niclosamide are difficult to investigate because they are usually not available commercially or they are quite expensive in the commercial market. In this study, the major metabolite of niclosamide in human liver microsomes (HLMs) was confirmed to be 3-OH niclosamide. Because the production of 3-OH niclosamide using HLMs has a slow turnover rate, a new method of producing niclosamide metabolite with an easier and highly cost-efficient method was thus conducted. Bacterial CYP102A1 (BM3) is one of the bacterial cytochrome P450s (CYPs) from Bacillus megaterium that structurally show similar activities to human CYPs. Here, the BM3 mutants were used to produce niclosamide metabolites and the metabolites were analyzed using high-performance liquid chromatography and LC-mass spectrometry. Among a set of mutants tested here, BM3 M14 mutant was the most active in producing 3-OH niclosamide, the major metabolite of niclosamide. Comparing BM3 M14 and HLMs, BM3 M14 production of 3-OH niclosamide was 34-fold higher than that of HLMs. Hence, the engineering of BM3 can be a cost-efficient method to produce 3-OH niclosamide.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19
/
Niclosamide
Limits:
Humans
Language:
English
Journal:
Enzyme Microb Technol
Year:
2023
Document Type:
Article
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