التفاصيل البيبلوغرافية
| العنوان: |
Evaluation of NfsA-like nitroreductases from Neisseria meningitidis and Bartonella henselae for enzyme-prodrug therapy, targeted cellular ablation, and dinitrotoluene bioremediation. |
| المؤلفون: |
Rich, Michelle H., Sharrock, Abigail V., Hall, Kelsi R., Ackerley, David F., MacKichan, Joanna K. |
| المصدر: |
Biotechnology Letters; Feb2018, Vol. 40 Issue 2, p359-367, 9p |
| مصطلحات موضوعية: |
NEISSERIA meningitidis, NITROREDUCTASES, BARTONELLA henselae, PRODRUGS, METRONIDAZOLE |
| مستخلص: |
Objectives: To characterize the activities of two candidate nitroreductases, Neisseria meningitidis NfsA (NfsA_Nm) and Bartonella henselae (PnbA_Bh), with the nitro-prodrugs, CB1954 and metronidazole, and the environmental pollutants 2,4- and 2,6-dinitrotoluene.Results: NfsA_Nm and PnbA_Bh were evaluated in Escherichia coli over-expression assays and as His6-tagged proteins in vitro. With the anti-cancer prodrug CB1954, both enzymes were more effective than the canonical O2-insensitive nitroreductase E. coli NfsB (NfsB_Ec), NfsA_Nm exhibiting comparable levels of activity to the leading nitroreductase candidate E. coli NfsA (NfsA_Ec). NfsA_Nm is also the first NfsA-family nitroreductase shown to produce a substantial proportion of 4-hydroxylamine end-product. NfsA_Nm and PnbA_Bh were again more efficient than NfsB_Ec at aerobic activation of metronidazole to a cytotoxic form, with NfsA_Nm appearing a promising candidate for improving zebrafish-targeted cell ablation models. NfsA_Nm was also more active than either NfsA_Ec or NfsB_Ec with 2,4- or 2,6-dinitrotoluene substrates, whereas PnbA_Bh was relatively inefficient with either substrate.Conclusions: NfsA_Nm is a promising new nitroreductase candidate for several diverse biotechnological applications. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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