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

Pierrel, Fabien; Burgardt, Arthur; Lee, Jinho; Pélosi, Ludovic; Wendisch, Volker F.

doi:10.1007/s11274-022-03242-3

Cited by 16 publications

(14 citation statements)

References 121 publications

(146 reference statements)

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“…There are currently no crystal structures available for eukaryotic homologs of COQ3. Structures are available for the orthologous O -methyltransferase UbiG from E. coli , which shares 34% sequence identity with human COQ3 and is part of a soluble ubiquinone/menaquinone biosynthetic complex [ 60 ]. Crystal structures of the apo and S-adenosyl-L-homocysteine (AdoHcy)-bound UbiG monomer have guided subsequent biochemical characterizations and confirmed its seven β-strand Rossmann-fold structure [ 45 , 46 ].…”

Section: Resultsmentioning

confidence: 99%

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Predicting and Understanding the Pathology of Single Nucleotide Variants in Human COQ Genes

Wang¹,

Jain²,

Novales³

et al. 2022

Antioxidants

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Coenzyme Q (CoQ) is a vital lipid that functions as an electron carrier in the mitochondrial electron transport chain and as a membrane-soluble antioxidant. Deficiencies in CoQ lead to metabolic diseases with a wide range of clinical manifestations. There are currently few treatments that can slow or stop disease progression. Primary CoQ10 deficiency can arise from mutations in any of the COQ genes responsible for CoQ biosynthesis. While many mutations in these genes have been identified, the clinical significance of most of them remains unclear. Here we analyzed the structural and functional impact of 429 human missense single nucleotide variants (SNVs) that give rise to amino acid substitutions in the conserved and functional regions of human genes encoding a high molecular weight complex known as the CoQ synthome (or Complex Q), consisting of the COQ3–COQ7 and COQ9 gene products. Using structures of COQ polypeptides, close homologs, and AlphaFold models, we identified 115 SNVs that are potentially pathogenic. Further biochemical characterizations in model organisms such as Saccharomyces cerevisiae are required to validate the pathogenicity of the identified SNVs. Collectively, our results will provide a resource for clinicians during patient diagnosis and guide therapeutic efforts toward combating primary CoQ10 deficiency.

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Section: Resultsmentioning

confidence: 99%

“…Nevertheless, it is worth noting that there are key differences in CoQ biosynthesis in E. coli and humans. UbiG is part of a soluble complex in the cytosol, while COQ3 is part of a membrane-associated complex in the mitochondrial matrix [ 60 ]. Implications of this membrane interaction in human COQ3 have not been investigated.…”

Section: Resultsmentioning

confidence: 99%

Predicting and Understanding the Pathology of Single Nucleotide Variants in Human COQ Genes

Wang¹,

Jain²,

Novales³

et al. 2022

Antioxidants

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“…Ubiquinone, commonly known as Coenzyme Q (CoQ), is a component of the respiratory chain in many prokaryotic organisms and is crucial for energy production as well as a variety of other intracellular activities. 71 Surprisingly, ubiquinone was found to be linked to bacterial pathogenicity in Francisella novicida and Xanthomonas campestris . 72 , 73 …”

Section: Resultsmentioning

confidence: 99%

Functional Analysis of Hypothetical Proteins of Vibrio parahaemolyticus Reveals the Presence of Virulence Factors and Growth-Related Enzymes With Therapeutic Potential

Shahrear

Zinnia

Sany

et al. 2022

Bioinform Biol Insights

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Vibrio parahaemolyticus, an aquatic pathogen, is a major concern in the shrimp aquaculture industry. Several strains of this pathogen are responsible for causing acute hepatopancreatic necrosis disease as well as other serious illness, both of which result in severe economic losses. The genome sequence of two pathogenic strains of V. parahaemolyticus, MSR16 and MSR17, isolated from Bangladesh, have been reported to gain a better understanding of their diversity and virulence. However, the prevalence of hypothetical proteins (HPs) makes it challenging to obtain a comprehensive understanding of the pathogenesis of V. parahaemolyticus. The aim of the present study is to provide a functional annotation of the HPs to elucidate their role in pathogenesis employing several in silico tools. The exploration of protein domains and families, similarity searches against proteins with known function, gene ontology enrichment, along with protein-protein interaction analysis of the HPs led to the functional assignment with a high level of confidence for 656 proteins out of a pool of 2631 proteins. The in silico approach used in this study was important for accurately assigning function to HPs and inferring interactions with proteins with previously described functions. The HPs with function predicted were categorized into various groups such as enzymes involved in small-compound biosynthesis pathway, iron binding proteins, antibiotics resistance proteins, and other proteins. Several proteins with potential druggability were identified among them. In addition, the HPs were investigated in search of virulent factors, which led to the identification of proteins that have the potential to be exploited as vaccine candidate. The findings of the study will be effective in gaining a better understanding of the molecular mechanisms of bacterial pathogenesis. They may also provide an insight into the process of evaluating promising targets for the development of drugs and vaccines against V. parahaemolyticus.

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“…In order to improve precursor supply for CoQ 10 production, overexpression of the MEP pathway genes dxs and idi is a common way to increase flux towards IPP and DMAPP and has been shown to increase patchoulol production in an engineered C. glutamicum strain [ 29 ]. Other strategies aim at the supply and distribution of the molecules of the MEP pathway entry point, glyceraldehyde 3-phosphate and pyruvate [ 54 ], e.g., by the modification of central carbon metabolism [ 55 ], CRISPRi-mediated repression [ 56 ], and increase in the NAD(P)H pool [ 57 ]. A different kind of approach is membrane engineering that involves the expression of proteins with membrane-bending properties and the overall increase in membrane synthesis to expand the membrane surface area and storage capacity for CoQ 10 .…”

Section: Discussionmentioning

confidence: 99%

Rational Engineering of Non-Ubiquinone Containing Corynebacterium glutamicum for Enhanced Coenzyme Q10 Production

et al. 2022

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Coenzyme Q10 (CoQ10) is a lipid-soluble compound with important physiological functions and is sought after in the food and cosmetic industries owing to its antioxidant properties. In our previous proof of concept, we engineered for CoQ10 biosynthesis the industrially relevant Corynebacterium glutamicum, which does not naturally synthesize any CoQ. Here, liquid chromatography–mass spectrometry (LC–MS) analysis identified two metabolic bottlenecks in the CoQ10 production, i.e., low conversion of the intermediate 10-prenylphenol (10P-Ph) to CoQ10 and the accumulation of isoprenologs with prenyl chain lengths of not only 10, but also 8 to 11 isopentenyl units. To overcome these limitations, the strain was engineered for expression of the Ubi complex accessory factors UbiJ and UbiK from Escherichia coli to increase flux towards CoQ10, and by replacement of the native polyprenyl diphosphate synthase IspB with a decaprenyl diphosphate synthase (DdsA) to select for prenyl chains with 10 isopentenyl units. The best strain UBI6-Rs showed a seven-fold increased CoQ10 content and eight-fold increased CoQ10 titer compared to the initial strain UBI4-Pd, while the abundance of CoQ8, CoQ9, and CoQ11 was significantly reduced. This study demonstrates the application of the recent insight into CoQ biosynthesis to improve metabolic engineering of a heterologous CoQ10 production strain.

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

Cited by 16 publications

References 121 publications

Predicting and Understanding the Pathology of Single Nucleotide Variants in Human COQ Genes

Predicting and Understanding the Pathology of Single Nucleotide Variants in Human COQ Genes

Functional Analysis of Hypothetical Proteins of Vibrio parahaemolyticus Reveals the Presence of Virulence Factors and Growth-Related Enzymes With Therapeutic Potential

Rational Engineering of Non-Ubiquinone Containing Corynebacterium glutamicum for Enhanced Coenzyme Q10 Production

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