Isovaleryl-CoA (IV-CoA) is usually derived from the degradation of leucine by using the Bkd (branched-chain keto acid dehydrogenase) complex. We have previously identified an alternative pathway for IV-CoA formation in myxobacteria that branches from the well-known mevalonate-dependent isoprenoid biosynthesis pathway. We identified 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase (MvaS) to be ...

Defects of cholesterol biosynthesis comprise a heterogeneous group of disorders, most of which have only been recently described and more are likely to follow in the near future. Mevalonic aciduria (MVA) and hyperimmunoglobulinemia D syndrome (HIDS) are due to allelic defects in mevalonate kinase, an enzyme located proximally in the pathway of cholesterol and nonsterol isoprene biosynthesis. Cl...

Abstract Paclitaxel (Taxol™), an alkaloid of diterpenoid family, is one the most widely used anti-cancer drugs due to its effectiveness against a variety tumors. Rather than directly extraction and chemical synthesis paclitaxel or intermediates from yew plants, construction microbial cell factory for biosynthesis will be more efficient sustainable. The challenge lies on insufficient precursor, ...

The cytosolic mevalonate (MVA) pathway in Hevea brasiliensis latex is the conventionally accepted pathway which provides isopentenyl diphosphate (IPP) for cis-polyisoprene (rubber) biosynthesis. However, the plastidic 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway may be an alternative source of IPP since its more recent discovery in plants. Quantitative RT-PCR (qRT-PCR) expression profiles ...

Hevea brasiliensis Müll. Arg. is a tree that produces natural rubber, an industrially vital isoprenoid polymer. Biosynthesis of natural rubber is known to take place biochemically by a mevalonate (MVA) pathway, but molecular biological characterization of related genes has been insufficient. From H. brasiliensis, we obtained full-length cDNA of genes encoding all of the enzymes that catalyze th...

Some bisphosphonates used for the treatment of bone disorders are also potent inhibitors of squalene synthase, a critical enzyme for sterol biosynthesis. Among seven drugs tested, YM 175 (cycloheptylaminomethylene-1,1-bisphosphonic acid) was the most potent inhibitor of rat liver microsomal squalene synthase (Ki = 57 nM) and sterol biosynthesis from [14C]mevalonate in rat liver homogenate (IC50...

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...

fenugreek (trigonella foenum-graecum l.) has a long and respected history of medicinal uses in middle east and persian medicine. the hypocholesterolaemic and hypoglycaemic effects of fenugreek were attributed to its major steroidal sapogenin, diosgenin and its major alkaloid, trigonelline. the knowledge of diosgenin and trigonelline biosynthesis is derived from studies of cholesterol and nicoti...

The mevalonate pathway, crucial for cholesterol synthesis, plays a key role in multiple cellular processes. Deregulation of this pathway is also correlated with diminished protein prenylation, an important post-translational modification necessary to localize certain proteins, such as small GTPases, to membranes. Mevalonate pathway blockade has been linked to mitochondrial dysfunction: especial...

Cells of innate immunity, mainly monocytes/macrophages, form a long-term nonspecific immunological memory during the initial encounter with pathogen, so-called trained immunity. Mevalonate pathway metabolites play an important role in formation The aim this investigation was to study effect modulators mevalonate pathway, and zoledronate, on immunity human animal monocytes/ macrophages. Material...