Shortcut for isoprenoid biosynthesis

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Isoprenoid biosynthesis in Plasmodium falciparum.

Malaria kills nearly 1 million people each year, and the protozoan parasite Plasmodium falciparum has become increasingly resistant to current therapies. Isoprenoid synthesis via the methylerythritol phosphate (MEP) pathway represents an attractive target for the development of new antimalarials. The phosphonic acid antibiotic fosmidomycin is a specific inhibitor of isoprenoid synthesis and has...

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Metabolic plasticity for isoprenoid biosynthesis in bacteria.

Isoprenoids are a large family of compounds synthesized by all free-living organisms. In most bacteria, the common precursors of all isoprenoids are produced by the MEP (methylerythritol 4-phosphate) pathway. The MEP pathway is absent from archaea, fungi and animals (including humans), which synthesize their isoprenoid precursors using the completely unrelated MVA (mevalonate) pathway. Because ...

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Two distinct pathways for essential metabolic precursors for isoprenoid biosynthesis

Isoprenoids are a diverse group of molecules found in all organisms, where they perform such important biological functions as hormone signaling (e.g., steroids) in mammals, antioxidation (e.g., carotenoids) in plants, electron transport (e.g., ubiquinone), and cell wall biosynthesis intermediates in bacteria. All isoprenoids are synthesized by the consecutive condensation of the five-carbon mo...

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Five Questions about Non-Mevalonate Isoprenoid Biosynthesis

Isoprenoids (also referred to as terpenoids) are the largest group of natural products, comprising over 25,000 known compounds [1]. Each member of this class is assembled from 5-carbon (C5) isoprene units and derived metabolically from the basic building block isopentenyl pyrophosphate (IPP) and its isomer, dimethylallyl pyrophosphate (DMAPP). Subsequent metabolic reactions (such as cyclization...

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Novel bisphosphonates as inhibitors of isoprenoid biosynthesis

Statins and nitrogenous bisphosphonates (NBPs) are clinically used inhibitors of the mevalonate pathway, which is the pathway responsible for cholesterol production as well as other isoprenoid-derived molecules. Through the inhibition of HMGCR and FDPS, respectively, these drugs deplete cells of FPP and can disrupt downstream cellular processes such as protein prenylation. At the major branch p...

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ژورنال

عنوان ژورنال: Nature Catalysis

سال: 2019

ISSN: 2520-1158

DOI: 10.1038/s41929-019-0240-8