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The sole unifying feature of Archaea is the use of isoprenoid-based glycerol lipid ethers to compose cellular membranes. The branched hydrocarbon tails of archaeal lipids are synthesized via the polymerization of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), but many questions still surround the pathway(s) that result in production of IPP and DMAPP in archaeal species. Isotopic-labeling strategies argue for multiple biological routes for production of mevalonate, but biochemical and bioinformatic studies support only a linear pathway for mevalonate production. Here, we use a combination of genetic and biochemical assays to detail the production of mevalonate in the model archaeon Thermococcus kodakarensis. We demonstrate that a single, linear pathway to mevalonate biosynthesis is essential and that alternative routes of mevalonate production, if present, are not biologically sufficient to support growth in the absence of the classical mevalonate pathway resulting in IPP production from acetyl-CoA. Archaeal species provide an ideal platform for production of high-value isoprenoids in large quantities, and the results obtained provide avenues to further increase the production of mevalonate to drive isoprenoid production in archaeal hosts.
This article was published in the following journal.
Name: Extremophiles : life under extreme conditions
Replication protein A (RPA) is an essential component of DNA metabolic processes. RPA binds to single-stranded DNA (ssDNA) and interacts with multiple DNA-binding proteins. In this study, we showed th...
The mevalonate pathway is essential for the synthesis of isoprenoids and cholesterol. Adipose tissue is known as a major site for cholesterol storage; however, the role of the local mevalonate pathwa...
Mevalonate is a useful metabolite synthesized from three molecules of acetyl-CoA, consuming two molecules of NADPH. Escherichia coli catabolizes glucose to acetyl-CoA via several routes, such as the E...
Mevalonate Kinase (MVK) catalyses the ATP-Mg2+ mediated phosphate transfer of mevalonate to produce mevalonate 5-phosphate and is a key kinase in the mevalonate pathway in the biosynthesis of isopente...
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A dihydroxy monocarboxylic acid and precursor in the biosynthetic pathway known as the mevalonate pathway, which produces terpenes and steroids that are vital for diverse cellular functions.
An enzyme involved in the MEVALONATE pathway, it catalyses the synthesis of farnesyl diphosphate from isopentenyl diphosphate and dimethylallyl diphosphate.
Compounds with a core of 10 carbons generally formed via the mevalonate pathway from the combination of 3,3-dimethylallyl pyrophosphate and isopentenyl pyrophosphate. They are cyclized and oxidized in a variety of ways. Due to the low molecular weight many of them exist in the form of essential oils (OILS, VOLATILE).
Autosomal recessive disorder caused by mutations in the mevalonate kinase gene. Because of the mutations cholesterol biosynthesis is disrupted and MEVALONIC ACID accumulates. It is characterized by a range of symptoms, including dysmorphic FACIES, psychomotor retardation, CATARACT, hepatosplenomegaly, CEREBELLAR ATAXIA, elevated IMMUNOGLOBULIN D, and recurrent febrile crises with FEVER; LYMPHADENOPATHY; ARTHRALGIA; EDEMA; and rash.
A technique of operations research for solving certain kinds of problems involving many variables where a best value or set of best values is to be found. It is most likely to be feasible when the quantity to be optimized, sometimes called the objective function, can be stated as a mathematical expression in terms of the various activities within the system, and when this expression is simply proportional to the measure of the activities, i.e., is linear, and when all the restrictions are also linear. It is different from computer programming, although problems using linear programming techniques may be programmed on a computer.
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...
Immunoassay - ELISA
Immunoassays are quick and accurate tests to detect specific molecules. Immunoassays rely on an antibody to bind to the specific structure of a molecule. Antibodies are proteins generated by animals in response to the invasion of a foreign molecule (anti...