A dedicated flavin-dependent monooxygenase catalyzes the hydroxylation of demethoxyubiquinone into ubiquinone (coenzyme Q) in Arabidopsis

Latimer, Scott; Keene, Shea A.; Stutts, Lauren R; Berger, A.; Bernert, Ann C.; Soubeyrand, Eric; Wright, Janet; Clarke, Catherine F.; Block, Anna; Colquhoun, Thomas A.; Elowsky, Christian; Christensen, Alan C.; Wilson, Mark A.; Basset, Gilles J.

doi:10.1016/j.jbc.2021.101283

Cited by 11 publications

(10 citation statements)

References 64 publications

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“…1 ). However, some variation exists since a new FMO has recently been demonstrated to replace Coq7 in land plants, green algae and apicomplexans (Latimer et al 2021 ; Xu et al 2021a ). The eukaryotic C1-hydroxylase is not yet known.…”

Section: Overview Of Coq Biosynthesis Pathways In Microorganismsmentioning

confidence: 99%

Recent advances in the metabolic pathways and microbial production of coenzyme Q

Pierrel

Burgardt

Lee

et al. 2022

World J Microbiol Biotechnol

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Coenzyme Q (CoQ) serves as an electron carrier in aerobic respiration and has become an interesting target for biotechnological production due to its antioxidative effect and benefits in supplementation to patients with various diseases. Here, we review discovery of the pathway with a particular focus on its superstructuration and regulation, and we summarize the metabolic engineering strategies for overproduction of CoQ by microorganisms. Studies in model microorganisms elucidated the details of CoQ biosynthesis and revealed the existence of multiprotein complexes composed of several enzymes that catalyze consecutive reactions in the CoQ pathways of Saccharomyces cerevisiae and Escherichia coli. Recent findings indicate that the identity and the total number of proteins involved in CoQ biosynthesis vary between species, which raises interesting questions about the evolution of the pathway and could provide opportunities for easier engineering of CoQ production. For the biotechnological production, so far only microorganisms have been used that naturally synthesize CoQ10 or a related CoQ species. CoQ biosynthesis requires the aromatic precursor 4-hydroxybenzoic acid and the prenyl side chain that defines the CoQ species. Up to now, metabolic engineering strategies concentrated on the overproduction of the prenyl side chain as well as fine-tuning the expression of ubi genes from the ubiquinone modification pathway, resulting in high CoQ yields. With expanding knowledge about CoQ biosynthesis and exploration of new strategies for strain engineering, microbial CoQ production is expected to improve.

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Section: Overview Of Coq Biosynthesis Pathways In Microorganismsmentioning

confidence: 99%

Recent advances in the metabolic pathways and microbial production of coenzyme Q

Pierrel

Burgardt

Lee

et al. 2022

World J Microbiol Biotechnol

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“…In this article, we demonstrate that the preorganized electric field exerts opposing effects on the two steps of the catalytic cycles of metalloenzymes. We focus on a recently characterized heme enzyme of l -tyrosine hydroxylases (TyrH), which catalyzes the aromatic hydroxylation of the substrate l -tyrosine (Tyr) to form the natural product intermediates l -3,4-dihydroxyphenylalanine (DOPA), , which is the rate-limiting step responsible for the biosynthesis of natural product catecholamines dopamine, norepinephrine, and epinephrine. − This kind of aromatic hydroxylation is common in the metabolism of xenobiotic compounds and in biosyntheses of natural products. − As shown in Scheme , the catalytic reactions of TyrH consist of two stages. The first stage involves the activation of H 2 O 2 to form the active species of Cpd I, while the second stage involves the Cpd I-mediated hydroxylation of l -Tyr to afford l -DOPA.…”

Section: Introductionmentioning

confidence: 99%

How Do Preorganized Electric Fields Function in Catalytic Cycles? The Case of the Enzyme Tyrosine Hydroxylase

et al. 2022

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Nature has devised intrinsic electric fields (IEFs) that are engaged in electrostatic catalysis of enzymes. But, how does the IEF target its function in enzymes that involve several reaction steps in catalytic cycles? To decipher the impact of the IEF on the catalytic cycle of an enzyme system, we have performed molecular dynamics and quantum-mechanical/molecular-mechanical (QM/MM) simulations on tyrosine hydroxylase (TyrH). The catalytic cycle of TyrH involves two reaction stages: the activation of H2O2 to form the active species of compound I (Cpd I), in the first stage, and the Cpd I-mediated hydroxylation of l-tyrosine to l-DOPA, in the second stage. For the first stage, the QM/MM calculations show that a heme-propionate group functions as a base to catalyze the O–O heterolysis reaction. For the second stage, the study reveals that the reaction is initiated by the His88-mediated proton-coupled electron transfer followed by the oxygen atom transfer from compound II (Cpd II) to the l-Tyr substrate. Importantly, our calculations demonstrate that the IEF in TyrH is optimized to promote the O–O bond heterolysis that generates the active species of the enzyme, Cpd I. However, the same IEF slows down the subsequent aromatic hydroxylation. Thus, the IEF in the TyrH enzymes does not catalyze the product formation step, but will selectively boost one or more challenging steps in the catalytic cycle. These findings have general implications on O2/H2O2-dependent metalloenzymes, which can expand our understanding of how nature has used electric fields as “smart reagents” in modulating the catalytic reactivity.

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“…We now report that excess Mn disrupts mitochondrial bioenergetics via an erroneous insertion of Mn in the diiron center of Coq7, revealing a unique sensitivity of a membrane-bound diiron carboxylate enzyme towards mismetallation. In contrast to fungi and animals, DMQ hydroxylation in plants and green algae is catalyzed by a flavin-dependent monooxygenase (CoqF) [61][62][63] , likely insensitive towards Mn accumulation. However, membrane-bound diiron carboxylate enzymes in plants include the MME hydroxylase, critical for chlorophyll biosynthesis, as well as the mitochondrial alternative oxidase (AOX) and the plastid terminal oxidase (PTOX), oxidizing ubiquinol and plastochinol, respectively 38 .…”

Section: Discussionmentioning

confidence: 99%

Manganese-driven CoQ deficiency

et al. 2022

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Overexposure to manganese disrupts cellular energy metabolism across species, but the molecular mechanism underlying manganese toxicity remains enigmatic. Here, we report that excess cellular manganese selectively disrupts coenzyme Q (CoQ) biosynthesis, resulting in failure of mitochondrial bioenergetics. While respiratory chain complexes remain intact, the lack of CoQ as lipophilic electron carrier precludes oxidative phosphorylation and leads to premature cell and organismal death. At a molecular level, manganese overload causes mismetallation and proteolytic degradation of Coq7, a diiron hydroxylase that catalyzes the penultimate step in CoQ biosynthesis. Coq7 overexpression or supplementation with a CoQ headgroup analog that bypasses Coq7 function fully corrects electron transport, thus restoring respiration and viability. We uncover a unique sensitivity of a diiron enzyme to mismetallation and define the molecular mechanism for manganese-induced bioenergetic failure that is conserved across species.

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A dedicated flavin-dependent monooxygenase catalyzes the hydroxylation of demethoxyubiquinone into ubiquinone (coenzyme Q) in Arabidopsis

Cited by 11 publications

References 64 publications

Recent advances in the metabolic pathways and microbial production of coenzyme Q

Recent advances in the metabolic pathways and microbial production of coenzyme Q

How Do Preorganized Electric Fields Function in Catalytic Cycles? The Case of the Enzyme Tyrosine Hydroxylase

Manganese-driven CoQ deficiency

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