Biosynthesis of Isoprenoids via Mevalonate in Archaea: The Lost Pathway

Smit, Arian F. A.; Mushegian, Arcady

doi:10.1101/gr.145600

Cited by 123 publications

(80 citation statements)

References 60 publications

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“…This ϽZ scoreϾ is considerably lower than the corresponding value obtained by comparing MDD-and HSK-derived alternative models, and presumably reflects the greater structural difference between IDI and MutT. Nonetheless, our structural comparison and modeling results do confirm the recently proposed similarity of the IDIs and the nudix proteins (32).…”

Section: Idi Resembles Muttcontrasting

confidence: 55%

Structural genomics of enzymes involved in sterol/isoprenoid biosynthesis

Bonanno

Edo

Eswar

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

114

104

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X-ray structures of two enzymes in the sterol͞isoprenoid biosynthesis pathway have been determined in a structural genomics pilot study. Mevalonate-5-diphosphate decarboxylase (MDD) is a single-domain ␣͞␤ protein that catalyzes the last of three sequential ATP-dependent reactions which convert mevalonate to isopentenyl diphosphate. Isopentenyl disphosphate isomerase (IDI) is an ␣͞␤ metalloenzyme that catalyzes interconversion of isopentenyl diphosphate and dimethylallyl diphosphate, which condense in the next step toward synthesis of sterols and a host of natural products. Homology modeling of related proteins and comparisons of the MDD and IDI structures with two other experimentally determined structures have shown that MDD is a member of the GHMP superfamily of small-molecule kinases and IDI is similar to the nudix hydrolases, which act on nucleotide diphosphatecontaining substrates. Structural models were produced for 379 proteins, encompassing a substantial fraction of both protein superfamilies. All three enzymes responsible for synthesis of isopentenyl diphosphate from mevalonate (mevalonate kinase, phosphomevalonate kinase, and MDD) share the same fold, catalyze phosphorylation of chemically similar substrates (MDD decarboxylation involves phosphorylation of mevalonate diphosphate), and seem to have evolved from a common ancestor. These structures and the structural models derived from them provide a framework for interpreting biochemical function and evolutionary relationships.H igh-throughput genome sequencing has dramatically expanded our knowledge of the proteins of the natural world. Next steps in understanding these macromolecules will involve studies of biochemical and biological function, depending critically on three-dimensional structural information. Nascent structural genomics efforts are aimed at developing experimental and computational pipelines for studying protein structure and integrating their results into the mainstream of biomedical research (1).

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Section: Idi Resembles Muttcontrasting

confidence: 55%

Structural genomics of enzymes involved in sterol/isoprenoid biosynthesis

Bonanno

Edo

Eswar

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

114

104

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“…While isoprenoids are found only in archaea as a component of polar lipids, more than 25,000 naturally occurring isoprenoid derivatives are known to exist throughout the organisms of the three domains. As isoprenoid biosynthesis is a more ordinary subject than the other aspects of the biosynthesis of archaeal polar lipids, the subject has been more extensively studied and reviewed (9,93). Therefore, this section is limited to Archaea-specific topics of isoprenoid biosynthesis.…”

Section: Isoprenoid Biosynthesismentioning

confidence: 99%

Biosynthesis of Ether-Type Polar Lipids in Archaea and Evolutionary Considerations

Koga

Morii

2007

Microbiol Mol Biol Rev

296

259

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SUMMARY This review deals with the in vitro biosynthesis of the characteristics of polar lipids in archaea along with preceding in vivo studies. Isoprenoid chains are synthesized through the classical mevalonate pathway, as in eucarya, with minor modifications in some archaeal species. Most enzymes involved in the pathway have been identified enzymatically and/or genomically. Three of the relevant enzymes are found in enzyme families different from the known enzymes. The order of reactions in the phospholipid synthesis pathway (glycerophosphate backbone formation, linking of glycerophosphate with two radyl chains, activation by CDP, and attachment of common polar head groups) is analogous to that of bacteria. sn-Glycerol-1-phosphate dehydrogenase is responsible for the formation of the sn-glycerol-1-phosphate backbone of phospholipids in all archaea. After the formation of two ether bonds, CDP-archaeol acts as a common precursor of various archaeal phospholipid syntheses. Various phospholipid-synthesizing enzymes from archaea and bacteria belong to the same large CDP-alcohol phosphatidyltransferase family. In short, the first halves of the phospholipid synthesis pathways play a role in synthesis of the characteristic structures of archaeal and bacterial phospholipids, respectively. In the second halves of the pathways, the polar head group-attaching reactions and enzymes are homologous in both domains. These are regarded as revealing the hybrid nature of phospholipid biosynthesis. Precells proposed by Wächtershäuser are differentiated into archaea and bacteria by spontaneous segregation of enantiomeric phospholipid membranes (with sn-glycerol-1-phosphate and sn-glycerol-3-phosphate backbones) and the fusion and fission of precells. Considering the nature of the phospholipid synthesis pathways, we here propose that common phospholipid polar head groups were present in precells before the differentiation into archaea and bacteria.

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“…In short, IPP isomerase is necessary for the biosynthesis of isoprenoid compounds via the mevalonate pathway, and unnecessary for that of the nonmevalonate pathway. However, despite the sole utilization of the mevalonate pathway for isoprenoid biosynthesis, many archaea and some bacteria lack homologues of IPP isomerase genes in their genome sequences [8].Kaneda et al recently cloned the gene fni from Streptomyces sp. strain CL190, which possesses genes of the mevalonate pathway as a cluster in addition to those of the nonmevalonate pathway [9].…”

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confidence: 99%

mentioning

confidence: 99%

Type 2 isopentenyl diphosphate isomerase from a thermoacidophilic archaeon Sulfolobus shibatae

Yamashita

Hemmi

Ikeda

et al. 2004

European Journal of Biochemistry

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Although isopentenyl diphosphate-dimethylallyl diphosphate isomerase is thought to be essential for archaea because they use the mevalonate pathway, its corresponding activity has not been detected in any archaea. A novel type of the enzyme, which has no sequence similarity to the known, well-studied type of enzymes, was recently reported in some bacterial strains. In this study, we describe the cloning of a gene of a homologue of the novel bacterial isomerase from a thermoacidophilic archaeon Sulfolobus shibatae. The gene was heterologously expressed in Escherichia coli, and the recombinant enzyme was purified and characterized. The thermostable archaeal enzyme is tetrameric, and requires NAD(P)H and Mg 2+ for activity, similar to its bacterial homologues. Using its apoenzyme, we were able to confirm that the archaeal enzyme is strictly dependent on FMN. Moreover, we provide evidence to show that the enzyme also has NADH dehydrogenase activity although it catalyzes the isomerase reaction without consuming any detectable amount of NADH.Keywords: isopentenyl diphosphate-dimethylallyl diphosphate isomerase; isoprenoid; archaea; flavoprotein; NADH dehydrogenase.Isoprenoid compounds are the most diverse family of metabolites found in nature. They are necessary for all living organisms because they are functional parts of important compounds, including vitamins, hormones, respiratory quinones, and archaeal membranes [1]. The majority of isoprenoid compounds are synthesized from linear prenyl diphosphates, which are formed via the consecutive condensation of isopentenyl diphosphate (IPP), the active isoprene C 5 -unit, to its highly electrophilic isomer dimethylallyl diphosphate (DMAPP).Isopentenyl diphosphate-dimethylallyl diphosphate isomerase (IPP isomerase; EC 5.3.3.2) catalyzes the interconversion of IPP and DMAPP and is a key enzyme in the biosynthesis of isoprenoids [2]. Based on studies using eukaryotes, IPP has been shown to be synthesized from acetyl-CoA via the well-known mevalonate pathway and is further converted to DMAPP by IPP isomerase [3]. On the other hand, many bacteria, green algae, and chloroplasts of higher plants have recently been shown to use a different isoprenoid biosynthetic pathway, which is referred to as the nonmevalonate pathway [4,5]. It has been reported that IPP and DMAPP are synthesized separately in Escherichia coli and that the IPP isomerase gene was not essential for this organism [6]. Synechocystis sp. strain PCC6803, which also utilizes the nonmevalonate pathway for the biosynthesis of isoprenoids, was shown to be deficient in IPP isomerase activity [7]. In short, IPP isomerase is necessary for the biosynthesis of isoprenoid compounds via the mevalonate pathway, and unnecessary for that of the nonmevalonate pathway. However, despite the sole utilization of the mevalonate pathway for isoprenoid biosynthesis, many archaea and some bacteria lack homologues of IPP isomerase genes in their genome sequences [8].Kaneda et al. recently cloned the gene fni from Streptomyces sp. strain C...

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Biosynthesis of Isoprenoids via Mevalonate in Archaea: The Lost Pathway

Cited by 123 publications

References 60 publications

Structural genomics of enzymes involved in sterol/isoprenoid biosynthesis

Structural genomics of enzymes involved in sterol/isoprenoid biosynthesis

Biosynthesis of Ether-Type Polar Lipids in Archaea and Evolutionary Considerations

Type 2 isopentenyl diphosphate isomerase from a thermoacidophilic archaeon Sulfolobus shibatae

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