A [4Fe-4S] cluster resides at the active center of phosphomevalonate dehydratase, a key enzyme in the archaeal modified mevalonate pathway

Komeyama, Mutsumi; Kanno, Kohsuke; Mino, Hiroyuki; Yasuno, Yoko; Shinada, Tetsuro; Ito, Tomokazu; Hemmi, Hisashi

doi:10.3389/fmicb.2023.1150353

Cited by 3 publications

(2 citation statements)

References 34 publications

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“…1). Interestingly, while the archaeal MVA pathway includes oxygensensitive Fe-S cluster enzymes [27][28][29][30] , the more recently-evolved eukaryotic MVA pathway does not contain Fe-S cluster enzymes.…”

Section: Isoprenoids and The Methylerythritol Phosphate Pathwaymentioning

confidence: 99%

“…Very interestingly, the archaeal MVA pathway uses an Fe-S cluster enzyme, phosphomevalonate dehydratase, whereas eukaryotes use an alternative non-Fe-S cluster enzyme at that step in the pathway 30 . This is fascinating because it indicates that the eukaryotic pathway has evolved away from oxygen sensitivity conferred by the Fe-S cluster enzymes, and as such is far more resilient to oxidative stress.…”

Section: Exploring the Significance Of Non-biosynthetic Roles For The...mentioning

confidence: 99%

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The methylerythritol phosphate pathway as an oxidative stress sense and response system

Perez-Gil,

Behrendorff,

Douw

et al. 2024

Nat Commun

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The methylerythritol phosphate (MEP) pathway is responsible for biosynthesis of the precursors of isoprenoid compounds in eubacteria and plastids. It is a metabolic alternative to the well-known mevalonate pathway for isoprenoid production found in archaea and eukaryotes. Recently, a role for the MEP pathway in oxidative stress detection, signalling, and response has been identified. This role is executed in part through the unusual cyclic intermediate, methylerythritol cyclodiphosphate (MEcDP). We postulate that this response is triggered through the oxygen sensitivity of the MEP pathway’s terminal iron-sulfur (Fe-S) cluster enzymes. MEcDP is the substrate of IspG, the first Fe-S cluster enzyme in the pathway; it accumulates under oxidative stress conditions and acts as a signalling molecule. It may also act as an antioxidant. Furthermore, evidence is emerging for a broader and highly nuanced role of the MEP pathway in oxidative stress responses, implemented through a complex system of differential regulation and sensitivity at numerous nodes in the pathway. Here, we explore the evidence for such a role (including the contribution of the Fe-S cluster enzymes and different pathway metabolites, especially MEcDP), the evolutionary implications, and the many questions remaining about the behaviour of the MEP pathway in the presence of oxidative stress.

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Section: Isoprenoids and The Methylerythritol Phosphate Pathwaymentioning

confidence: 99%

Section: Exploring the Significance Of Non-biosynthetic Roles For The...mentioning

confidence: 99%

The methylerythritol phosphate pathway as an oxidative stress sense and response system

Perez-Gil,

Behrendorff,

Douw

et al. 2024

Nat Commun

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Production of the sesquiterpene bisabolene from one-carbon compounds in an engineeredMethanosarcina acetivorans

Mentrup,

Scheitz,

Wallenfang

et al. 2024

Preprint

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The isoprenoid bisabolene, one of the simplest monocyclic sesquiterpenes, is a natural plant product that, in addition to its biological function, serves as a precursor for many industrial products. Due to the low concentration of bisabolene and the long harvest cycle, industrial production of this isoprenoid in plants is economically challenging. Chemical synthesis of bisabolene also suffers from significant disadvantages, such as low yields, toxic side products and high costs. Archaea appear suitable producers of isoprenoids, as their membrane lipids consist of isoprenoid ethers, which are synthesized via a variant of the mevalonate pathway. Archaeal model species have versatile metabolic capacities, which makes them suitable candidates for biotechnological applications. Here, we engineeredMethanosarcina acetivoransfor production ofα-bisabolene from one-carbon substrates by introducing a bisabolene synthase fromAbies grandis. Expression of a codon-optimized bisabolene synthase gene in aM. acetivoranswild-type strain resulted in 10.6 mg bisabolene/liter of culture. Overexpressing genes of the mevalonate pathway only slightly increased bisabolene yields, which, however, were reached much earlier during incubations than in the corresponding wild-type strain. The data presented argue for the suitability ofM. acetivoransfor the biotechnical production of certain isoprenoids.

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Archaeal mevalonate pathway in the uncultured bacterium Candidatus Promineifilum breve belonging to the phylum Chloroflexota

Kanno,

Kuriki,

Yasuno

et al. 2024

Appl Environ Microbiol

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The archaeal mevalonate pathway is a recently discovered modified version of the eukaryotic mevalonate pathway. This pathway is widely conserved in archaea, except for some archaeal lineages possessing the eukaryotic or other modified mevalonate pathways. Although the pathway seems almost exclusive to the domain Archaea, the whole set of homologous genes of the pathway is found in the metagenome-assembled genome sequence of an uncultivated bacterium, Candidatus Promineifilum breve, of the phylum Chloroflexota. To prove the existence of the archaea-specific pathway in the domain Bacteria, we confirmed the activities of the enzymes specific to the pathway, phosphomevalonate dehydratase and anhydromevalonate phosphate decarboxylase, because only these two enzymes are absent in closely related Chloroflexota bacteria that possess a different type of modified mevalonate pathway. The activity of anhydromevalonate phosphate decarboxylase was evaluated by carotenoid production via the archaeal mevalonate pathway reconstituted in Escherichia coli cells, whereas that of phosphomevalonate dehydratase was confirmed by an in vitro assay using the recombinant enzyme after purification and iron-sulfur cluster reconstruction. Phylogenetic analyses of some mevalonate pathway-related enzymes suggest an evolutionary route for the archaeal mevalonate pathway in Candidatus P. breve, which probably involves horizontal gene transfer events. IMPORTANCE The recent discovery of various modified mevalonate pathways in microorganisms, such as archaea and Chloroflexota bacteria, has shed light on the complexity of the evolution of metabolic pathways, including those involved in primary metabolism. The fact that the archaeal mevalonate pathway, which is almost exclusive to the domain Archaea, exists in a Chloroflexota bacterium provides valuable insights into the molecular evolution of the mevalonate pathways and associated enzymes. Putative genes probably involved in the archaeal mevalonate pathway have also been found in the metagenome-assembled genomes of Chloroflexota bacteria. Such genes can contribute to metabolic engineering for the bioproduction of valuable isoprenoids because the archaeal mevalonate pathway is known to be an energy-saving metabolic pathway that consumes less ATP than other mevalonate pathways do.

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A [4Fe-4S] cluster resides at the active center of phosphomevalonate dehydratase, a key enzyme in the archaeal modified mevalonate pathway

Cited by 3 publications

References 34 publications

The methylerythritol phosphate pathway as an oxidative stress sense and response system

The methylerythritol phosphate pathway as an oxidative stress sense and response system

Production of the sesquiterpene bisabolene from one-carbon compounds in an engineeredMethanosarcina acetivorans

Archaeal mevalonate pathway in the uncultured bacterium Candidatus Promineifilum breve belonging to the phylum Chloroflexota

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