1887

Abstract

Flavonoids comprise a large group of bioactive polyphenolic plant secondary metabolites. Several of these possess potent activity against and , targeting enzymes involved in fatty acid biosynthesis, such as enoyl-ACP-reductase, -ketoacyl-ACP reductase and -hydroxyacyl-ACP dehydratase. Herein, we report that butein, isoliquirtigenin, 2,2′,4′-trihydroxychalcone and fisetin inhibit the growth of BCG. Furthermore, inhibition of the mycolic-acid-producing fatty acid synthase II (FAS-II) of suggests a mode of action related to those observed in and . Through a bioinformatic approach, we have established the product of as a candidate for the unknown mycobacterial dehydratase, and its overexpression in BCG conferred resistance to growth inhibition by butein and isoliquirtigenin, and relieved inhibition of fatty acid and mycolic acid biosynthesis . Furthermore, after overexpression of in , FAS-II was less sensitive to these inhibitors . Overall, the data suggest that these flavonoids are inhibitors of mycobacterial FAS-II and in particular Rv0636, which represents a strong candidate for the -hydroxyacyl-ACP dehydratase enzyme of FAS-II.

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2007-10-01
2020-08-15
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