of Isoprenoids Via the Non-mevalonate Pathway"

The mevalonate pathway and the glyceraldehyde 3-phosphate (GAP)–pyruvate pathway are alternative routes for the biosynthesis of the central isoprenoid precursor, isopentenyl diphosphate. Genomic analysis revealed that the staphylococci, streptococci, and enterococci possess genes predicted to encode all of the enzymes of the mevalonate pathway and not the GAP-pyruvate pathway, unlike Bacillus subtilis and most gram-negative bacteria studied, which possess only components of the latter pathway. Phylogenetic and comparative genome analyses suggest that the genes for mevalonate biosynthesis in gram-positive cocci, which are highly divergent from those of mammals, were horizontally transferred from a primitive eukaryotic cell. Enterococci uniquely encode a bifunctional protein predicted to possess both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and acetyl-CoA acetyltransferase activities. Genetic disruption experiments have shown that five genes encoding proteins involved in this pathway (HMG-CoA synthase, HMG-CoA reductase, mevalonate kinase, phosphomevalonate kinase, and mevalonate diphosphate decarboxylase) are essential for the in vitro growth of Streptococcus pneumoniae under standard conditions. Allelic replacement of the HMG-CoA synthase gene rendered the organism auxotrophic for mevalonate and severely attenuated in a murine respiratory tract infection model. The mevalonate pathway thus represents a potential antibacterial target in the low-G+C gram-positive cocci.

Biochemistry of the non-mevalonate isoprenoid pathway

of isoprenoids via the non-mevalonate pathway.

isoprenoids via the non-mevalonate pathway ..

The non-mevalonate pathway or2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose5-phosphate pathway (MEP/DOXP pathway) ofisoprenoid biosynthesis is an alternative metabolic pathway leadingto the formation of (IPP) and (DMAPP) that has been elucidated only recently.

"Review Biosynthesis of isoprenoids via the non ..

In contrast to the classical of isoprenoidbiosynthesis, and such as parasites have theability to produce their () using analternative pathway, the non-mevalonate pathway,which takes place in their . Inaddition, most including important pathogens such as synthesize IPP and DMAPP via thenon-mevalonate pathway.

In contrast to the classical mevalonate pathway of isoprenoid biosynthesis, ..
The Non-Mevalonate Pathway to Isoprenoid Biosynthesis : ..

Biosynthesis of isoprenoids via mevalonate in Archaea: …

All isoprenoids are assembled using two common five-carbon precursors, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) that are biosynthesized via two completely independent routes: the mevalonate and the non-mevalonate pathway.

mevalonate pathway of isoprenoid biosynthesis, ..

Biosynthesis of isoprenoids via the non-mevalonate pathway…

The low-G+C gram-positive cocci are major pathogens, and novel targets for drug intervention are required to circumvent the resistance mechanisms which compromise current antibacterial agents. In a search for such novel drug targets, five full-length genes encoding enzymes that are predicted to catalyze consecutive steps in the mevalonate pathway for IPP biosynthesis were identified in seven species of gram-positive cocci. The nucleotide and derived amino acid sequences of HMG-CoA synthase, mevalonate kinase, phosphomevalonate kinase, and mevalonate diphosphate decarboxylase have not previously been identified in bacteria other than Borrelia burgdorferi, and the amino acid sequences of streptococcal biosynthetic HMG-CoA reductases have been reported only recently (). None of the species possessed homologs of the genes identified in the GAP-pyruvate pathway for IPP synthesis other than ygbP, suggesting that isoprenoids are synthesized in the streptococci, staphylococci, and enterococci solely via the mevalonate pathway.

biosynthesis of isoprenoids via mevalonate.

in the biosynthesis of isoprenoids via mevalonate.

Incorporation of 13C-labeled glycerol or pyruvate into the ubiquinone Q8 of mutants lacking enzymes of the triose phosphate metabolism and of (U-13C6)glucose into the triterpenoids of the hopane series of showed that glyceraldehyde 3-phosphate (or eventually glyceraldehyde) and a C2 unit derived from pyruvate decarboxylation were the only precursors of the C5 skeleton of isoprenic units in a novel non-mevalonate pathway for isoprenoid biosynthesis in these bacteria.