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Molecules 2016, 21(5), 654;

Flavin-Dependent Thymidylate Synthase as a New Antibiotic Target

Department of Chemistry, The University of Iowa, Iowa City, IA 52242-1727, USA
Author to whom correspondence should be addressed.
Academic Editor: Jean Jacques Vanden Eynde
Received: 6 April 2016 / Revised: 9 May 2016 / Accepted: 13 May 2016 / Published: 20 May 2016
PDF [2246 KB, uploaded 20 May 2016]


In humans de novo synthesis of 2′-deoxythymidine-5′-monophosphate (dTMP), an essential building block of DNA, utilizes an enzymatic pathway requiring thymidylate synthase (TSase) and dihydrofolate reductase (DHFR). The enzyme flavin-dependent thymidylate synthase (FDTS) represents an alternative enzymatic pathway to synthesize dTMP, which is not present in human cells. A number of pathogenic bacteria, however, depend on this enzyme in lieu of or in conjunction with the analogous human pathway. Thus, inhibitors of this enzyme may serve as antibiotics. Here, we review the similarities and differences of FDTS vs. TSase including aspects of their structure and chemical mechanism. In addition, we review current progress in the search for inhibitors of flavin dependent thymidylate synthase as potential novel therapeutics. View Full-Text
Keywords: flavin; enzyme; mechanism; thymidylate synthase; antibiotic flavin; enzyme; mechanism; thymidylate synthase; antibiotic

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Choi, M.; Karunaratne, K.; Kohen, A. Flavin-Dependent Thymidylate Synthase as a New Antibiotic Target. Molecules 2016, 21, 654.

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