Inhibition of the Non-Mevalonate 1-Deoxy-ᴅ-xylulose-5-phosphate Pathway of Plant Isoprenoid Biosynthesis by Fosmidomycin

Abstract

Various bacterial and plastidic plant terpenoids are synthesized via the non-mevalonate1-deoxy-ᴅ-xylulose-5-phosphate (DOXP) pathway. The antibiotic and herbicidal compound fosmidomycin is known to inhibit growth of several bacteria and plants, but so far its mode of action was unknown. Here we present data which demonstrate that the DOXP pathway of isoprenoid biosynthesis is efficiently blocked by fosmidomycin. The results point to the DOXP reductoisom erase as the probable target enzyme of fosmidomycin.

Increased Thermostability of Thylakoid Membranes in Isoprene-Emitting Leaves Probed with Three Biophysical Techniques

“…To inhibit isoprene emission from Platanus leaves, fosmidomycin, a specific inhibitor of 2-deoxyxylulose 5-phosphate reductoisomerase (Zeidler et al, 1998), was used. Platanus leaves were cut under water and maintained with the petiole in a glass vial with 15 mL of distilled water for 1 h. Fosmidomycin (5 mM) was then added to the water and taken up by the leaf through transpiration stream.…”

An Escherichia coli undecaprenyl-pyrophosphate phosphatase implicated in undecaprenyl phosphate recycling

“…Fosmidomycin (Fm) is an antibiotic that specifically inhibits the conversion of deoxy-xylulose 5-phosphate into methylerythritol 4-phosphate (Kuzuyama et al, 1998a;Zeidler et al, 1998), the second step in the Und-PP de novo synthesis pathway (Kuzuyama et al, 1998b;RodriguezConcepcion & Boronat, 2002;Takahashi et al, 1998). We reasoned that in comparison to the parental strain, E. coli uppP mutants with additional defects in the Und-PP recycling pathway would exhibit higher susceptibility to Fm since de novo synthesis of Und-P and recycling of Und-PP would both be compromised.…”

Synthesis of α‐Substituted Fosmidomycin Analogues as Highly Potent Plasmodium falciparum Growth Inhibitors.

“…Previous studies demonstrated that fosmidomycin exerts potent antimalarial activity by inhibition of DOXP reductoisomerase (DXR), the second enzyme in the reaction cascade. 6,7 In recent clinical trials conducted in Gabon and Thailand, fosmidomycin proved to be efficient in the treatment of patients suffering from acute, uncomplicated P. falciparum malaria. 8,9 Fosmidomycin has the advantage to be remarkably nontoxic and to exhibit activity against multiresistant parasite strains.…”