Coenzyme Q Biosynthesis: An Update on the Origins of the Benzenoid Ring and Discovery of New Ring Precursors.
14 Jun 2021-Metabolites (Multidisciplinary Digital Publishing Institute)-Vol. 11, Iss: 6, pp 385-385
TL;DR: In this paper, stable isotope labeling has been used to delineate the biosynthetic pathways leading to CoQ in E. coli, yeast, and plant and animal cells.
Abstract: Coenzyme Q (ubiquinone or CoQ) is a conserved polyprenylated lipid essential for mitochondrial respiration. CoQ is composed of a redox-active benzoquinone ring and a long polyisoprenyl tail that serves as a membrane anchor. A classic pathway leading to CoQ biosynthesis employs 4-hydroxybenzoic acid (4HB). Recent studies with stable isotopes in E. coli, yeast, and plant and animal cells have identified CoQ intermediates and new metabolic pathways that produce 4HB. Stable isotope labeling has identified para-aminobenzoic acid as an alternate ring precursor of yeast CoQ biosynthesis, as well as other natural products, such as kaempferol, that provide ring precursors for CoQ biosynthesis in plants and mammals. In this review, we highlight how stable isotopes can be used to delineate the biosynthetic pathways leading to CoQ.
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TL;DR: A review of the discovery of the CoQ pathway with a particular focus on its superstructuration and regulation is presented in this article , where the authors summarize the metabolic engineering strategies for overproduction of CoQ by microorganisms.
Abstract: Abstract 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 CoQ 10 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.
11 citations
TL;DR: In this article , it was shown that plants derive approximately a quarter of 4-hydroxybenzoate, which serves as the direct ring precursor of ubiquinone, from the catabolism of kaempferol.
8 citations
TL;DR: In this paper , the cytosolic lipid transfer protein STARD7 is identified as a critical factor of intracellular coenzyme Q transport and suppressor of ferroptosis.
Abstract: Coenzyme Q (or ubiquinone) is a redox-active lipid that serves as universal electron carrier in the mitochondrial respiratory chain and antioxidant in the plasma membrane limiting lipid peroxidation and ferroptosis. Mechanisms allowing cellular coenzyme Q distribution after synthesis within mitochondria are not understood. Here we identify the cytosolic lipid transfer protein STARD7 as a critical factor of intracellular coenzyme Q transport and suppressor of ferroptosis. Dual localization of STARD7 to the intermembrane space of mitochondria and the cytosol upon cleavage by the rhomboid protease PARL ensures the synthesis of coenzyme Q in mitochondria and its transport to the plasma membrane. While mitochondrial STARD7 preserves coenzyme Q synthesis, oxidative phosphorylation function and cristae morphogenesis, cytosolic STARD7 is required for the transport of coenzyme Q to the plasma membrane and protects against ferroptosis. A coenzyme Q variant competes with phosphatidylcholine for binding to purified STARD7 in vitro. Overexpression of cytosolic STARD7 increases ferroptotic resistance of the cells, but limits coenzyme Q abundance in mitochondria and respiratory cell growth. Our findings thus demonstrate the need to coordinate coenzyme Q synthesis and cellular distribution by PARL-mediated STARD7 processing and identify PARL and STARD7 as promising targets to interfere with ferroptosis.
7 citations
TL;DR: Truffles are appreciated as food all over the world because of their extraordinary aroma, however, quantities are limited and successful cultivation in plantations is very labor-intensive and expensive, or even...
Abstract: Truffles are appreciated as food all over the world because of their extraordinary aroma. However, quantities are limited and successful cultivation in plantations is very labor-intensive and expensive, or even impossible for some species. These factors make truffles a very valuable food, which is why it is particularly rewarding and tempting to declare inferior species of truffles as more expensive species and thereby counterfeit them. The various species differ in their aroma and thus in their culinary value, but the adulterations cannot be detected on the basis of pure morphology. For this reason, the objective of the present study was to develop a non-targeted lipidomics approach using ion mobility spectrometry-mass spectrometry to distinguish between the white truffle species Tuber magnatum and T. borchii as well as the black truffle species T. melanosporum, T. aestivum and T. indicum. Several hundred features were detected, which were present in significantly different concentrations in the studied truffle species. The most important of them were identified using MS/MS spectra and collision cross section (CCS) values. Some compounds were detected whose CCS values have not yet been published and may facilitate identification by other researchers in the future. Just a few marker substances are sufficient to be able to distinguish both black and white truffle species with 100% accuracy. These results can be used for the development of rapid tests, which in the best case will allow truffle analysis directly on-site.
5 citations
TL;DR: In this paper, a review of animal models available for CoQ deficiency is presented, remarking on the most important outcomes and future research directions related to CoQ metabolism and how the current and novel animal models may help in the development of future research studies.
Abstract: Coenzyme Q (CoQ) is a vital lipophilic molecule that is endogenously synthesized in the mitochondria of each cell. The CoQ biosynthetic pathway is complex and not completely characterized, and it involves at least thirteen catalytic and regulatory proteins. Once it is synthesized, CoQ exerts a wide variety of mitochondrial and extramitochondrial functions thank to its redox capacity and its lipophilicity. Thus, low levels of CoQ cause diseases with heterogeneous clinical symptoms, which are not always understood. The decreased levels of CoQ may be primary caused by defects in the CoQ biosynthetic pathway or secondarily associated with other diseases. In both cases, the pathomechanisms are related to the CoQ functions, although further experimental evidence is required to establish this association. The conventional treatment for CoQ deficiencies is the high doses of oral CoQ10 supplementation, but this therapy is not effective for some specific clinical presentations, especially in those involving the nervous system. To better understand the CoQ biosynthetic pathway, the biological functions linked to CoQ and the pathomechanisms of CoQ deficiencies, and to improve the therapeutic outcomes of this syndrome, a variety of animal models have been generated and characterized in the last decade. In this review, we show all the animal models available, remarking on the most important outcomes that each model has provided. Finally, we also comment some gaps and future research directions related to CoQ metabolism and how the current and novel animal models may help in the development of future research studies.
4 citations
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TL;DR: It is concluded that better performed in vivo intervention and in vitro mechanistic studies are needed to fully understand how (poly)phenol molecules interact with human physiological and pathological processes.
Abstract: Human intervention trials have provided evidence for protective effects of various (poly)phenol-rich foods against chronic disease, including cardiovascular disease, neurodegeneration, and cancer. While there are considerable data suggesting benefits of (poly)phenol intake, conclusions regarding their preventive potential remain unresolved due to several limitations in existing studies. Bioactivity investigations using cell lines have made an extensive use of both (poly)phenolic aglycones and sugar conjugates, these being the typical forms that exist in planta, at concentrations in the low-μM-to-mM range. However, after ingestion, dietary (poly)phenolics appear in the circulatory system not as the parent compounds, but as phase II metabolites, and their presence in plasma after dietary intake rarely exceeds nM concentrations. Substantial quantities of both the parent compounds and their metabolites pass to the colon where they are degraded by the action of the local microbiota, giving rise principally to small phenolic acid and aromatic catabolites that are absorbed into the circulatory system. This comprehensive review describes the different groups of compounds that have been reported to be involved in human nutrition, their fate in the body as they pass through the gastrointestinal tract and are absorbed into the circulatory system, the evidence of their impact on human chronic diseases, and the possible mechanisms of action through which (poly)phenol metabolites and catabolites may exert these protective actions. It is concluded that better performed in vivo intervention and in vitro mechanistic studies are needed to fully understand how these molecules interact with human physiological and pathological processes.
1,968 citations
TL;DR: The chemistry and biochemistry of polyphenols as related to classification, extraction, separation and analytical methods, their occurrence and biosynthesis in plants, and the biological activities and implications in human health are reviewed.
Abstract: Polyphenols are the biggest group of phytochemicals, and many of them have been found in plant-based foods. Polyphenol-rich diets have been linked to many health benefits. This paper is intended to review the chemistry and biochemistry of polyphenols as related to classification, extraction, separation and analytical methods, their occurrence and biosynthesis in plants, and the biological activities and implications in human health. The discussions are focused on important and most recent advances in the above aspects, and challenges are identified for future research.
1,674 citations
TL;DR: A review on the chemistry and biochemistry of dietary polyphenols, their antioxidant and anti-inflammatory activities, and the underlying molecular mechanisms of their involvement in inflammation mediated metabolic diseases are also discussed in this article.
Abstract: Phenolic compounds including phenolic acids, flavonoids and proanthocyanidins are widely distributed in plants as a protective mechanism against biotic and abiotic stresses. Fruits, vegetables, grains, spices and herbs are the richest source of dietary polyphenols. High intake of these foods has been linked to lowered risk of most common degenerative and chronic diseases that are known to be caused by oxidative stress. This review intends to summarize briefly recent progress on the chemistry and biochemistry of dietary polyphenols, their antioxidant and anti-inflammatory activities, and the underlying molecular mechanisms of their involvement in inflammation mediated metabolic diseases are also discussed. Perspectives for future research are also briefly discussed.
936 citations
TL;DR: This review summarizes the findings available to day concerning CoQ distribution, biosynthesis, regulatory modifications and its participation in cellular metabolism.
919 citations
TL;DR: The MVA pathway is likely an ancestral metabolic route in all the three domains of life, and hence, it was probably present in the last common ancestor of all organisms (the cenancestor), and open the possibility that the cenANCestor had membranes containing isoprenoids.
Abstract: Isoprenoids are a very diverse family of organic compounds widespread in the three domains of life. Although they are produced from the condensation of the same precursors in all organisms (isopentenyl pyrophosphate and dimethylallyl diphosphate), the evolutionary origin of their biosynthesis remains controversial. Two independent nonhomologous metabolic pathways are known: the mevalonate (MVA) pathway in eukaryotes and archaea and the methylerythritol phosphate (MEP) pathway in bacteria and several photosynthetic eukaryotes. The MVA pathway is also found in a few bacteria, what has been explained in previous works by recent acquisition by horizontal gene transfer (HGT) from eukaryotic or archaeal donors. To reconsider the question of the evolutionary origin of the MVA pathway, we have studied the origin and the evolution of the enzymes of this pathway using phylogenomic analyses upon a taxon-rich sequence database. On the one hand, our results confirm the conservation in archaea of an MVA pathway partially different from eukaryotes. This implies that each domain of life possesses a characteristic major isoprenoid biosynthesis pathway: the classical MVA pathway in eukaryotes, a modified MVA pathway in archaea, and the MEP pathway in bacteria. On the other hand, despite the identification of several HGT events, our analyses support that the MVA pathway was ancestral not only in archaea and eukaryotes but also in bacteria, in contradiction with previous claims that the presence of this pathway in bacteria was due to HGT from other domains. Therefore, the MVA pathway is likely an ancestral metabolic route in all the three domains of life, and hence, it was probably present in the last common ancestor of all organisms (the cenancestor). These findings open the possibility that the cenancestor had membranes containing isoprenoids.
279 citations