Production of ubiquinone-10 using bacteria.

Yoshida, Hajime; Kotani, Yukinobu; Ochiai, Keiko; Araki, Kazumi

doi:10.2323/jgam.44.19

Cited by 103 publications

(69 citation statements)

References 13 publications

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“…For instance, recent studies have found that human patients suffering from nephrotic syndrome displayed reduced Q10 levels 42 , and a mutation in a Q10 biosynthetic enzyme in mice caused pathological symptoms similar to Parkinson's disease 43 . Finally, induction of Q8 accumulation by elevated salt levels might be an effective strategy for the biotechnological production of this or related compounds 44 . 50 mM NaCl and 450 mM NaCl, inferred from absolute quantification using lipid standards and 13 Clabeled internal metabolite standard for matrix effect correction.…”

Section: Discussionmentioning

confidence: 99%

Ubiquinone accumulation improves osmotic-stress tolerance in Escherichia coli

2014

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Bacteria are thought to cope with fluctuating environmental solute concentrations primarily by adjusting the osmolality of their cytoplasm. To obtain insights into underlying metabolic adaptions, we analyzed the global metabolic response of Escherichia coli to sustained hyperosmotic stress using non-targeted mass spectrometry. We observed that 52% of 1,071 detected metabolites, including known osmoprotectants, changed abundance with increasing salt challenge. Unexpectedly, unsupervised data analysis revealed a substantial increase of most intermediates in the ubiquinone-8 (Q8) biosynthesis pathway and a 110-fold accumulation of Q8 itself, as confirmed by quantitative lipidomics. We then demonstrate that Q8 is necessary for acute and sustained osmotic stress tolerance using Q8 mutants and tolerance rescue through feeding non-respiratory Q8 analogues. Finally, in vitro experiments with artificial liposomes reveal mechanical membrane stabilization as a principal mechanism of Q8-mediated osmoprotection. Thus, we find that besides regulating intracellular osmolality, E. coli enhances its cytoplasmic membrane stability to withstand osmotic stress. AbstractBacteria are thought to cope with fluctuating environmental solute concentrations primarily by adjusting the osmolality of their cytoplasm. To obtain insights into underlying metabolic adaptions, we analyzed the global metabolic response of Escherichia coli to sustained hyperosmotic stress using non-targeted mass spectrometry. We observed that 52% of 1,071 detected metabolites, including known osmoprotectants, changed abundance with increasing salt challenge. Unexpectedly, unsupervised data analysis revealed a substantial increase of most intermediates in the ubiquinone-8 (Q8) biosynthesis pathway and a 110-fold accumulation of Q8 itself, as confirmed by quantitative lipidomics. We then demonstrate that Q8 is necessary for acute and sustained osmotic stress tolerance using Q8 mutants and tolerance rescue through feeding non-respiratory Q8 analogues.Finally, in vitro experiments with artificial liposomes reveal mechanical membrane stabilization as a principal mechanism of Q8-mediated osmoprotection. Thus, we find that besides regulating intracellular osmolality, E. coli enhances its cytoplasmic membrane stability to withstand osmotic stress.

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Section: Discussionmentioning

confidence: 99%

Ubiquinone accumulation improves osmotic-stress tolerance in Escherichia coli

2014

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“…Due to reduced pigmentation, UF16 was thought to be deficient in carotenoid production. The reduced accumulation of carotenoid pigments in enhanced CoQ 10 producing R. sphaeroides [14,47] indicated the allocation of more cellular isoprenoid resources towards CoQ 10 production. Further investigation is required to correlate the relative distribution of isoprenoid flux to carotenoids and CoQ 10 biosynthetic pathway in UF16.…”

Section: Morphological and Physiological Characterization Of Mutant Uf16mentioning

confidence: 99%

“…Mutagenesis process using low-energy ion beam irradiation [11], menadione [12], high hydrostatic pressure treatment, UV and diethyl sulfate [13] have been reported for CoQ 10 strain improvement of bacterial strains. For rational selection of CoQ 10 overproducing bacterial mutants, the inhibitors like L-ethionine, daunomycin, menadione, vitamin K3 and sodium azide have been used [13,14]. These induced mutants showed improvements in CoQ 10 yield, but there are no reports on molecular characterization of these mutants to differentiate it from the original parent strains.…”

Section: Introductionmentioning

confidence: 99%

Morphological and Molecular Differentiation of Sporidiobolus johnsonii ATCC 20490 and Its Coenzyme Q10 Overproducing Mutant Strain UF16

et al. 2014

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Coenzyme Q 10 (CoQ 10 ) is an industrially important molecule having nutraceutical and cosmeceutical applications. CoQ 10 is mainly produced by microbial fermentation and the process demands the use of strains with high productivity and yields of CoQ 10 . During strain improvement program consisting of sequential induced mutagenesis, rational selection and screening process, a mutant strain UF16 was generated from Sporidiobolus johnsonii ATCC 20490 with 2.3-fold improvements in CoQ 10 content. EMS and UV rays were used as mutagenic agents for generating UF16 and it was rationally selected based on atorvastatin resistance as well as survival at free radicals exposure. We investigated the genotypic and phenotypic changes in UF16 in order to differentiate it from wild type strain. Morphologically it was distinct due to reduced pigmentation of colony, reduced cell size and significant reduction in mycelial growth forms with abundance of yeast forms. At molecular level, UF16 was differentiated based on PCR fingerprinting method of RAPD as well as large and small-subunit rRNA gene sequences.Rapid molecular technique of RAPD analysis using six primers showed 34 % polymorphic fragments with mean genetic distance of 0.235. The partial sequences of rRNAgene revealed few mutation sites on nucleotide base pairs. However, the mutations detected on rRNA gene of UF16 were less than 1 % of total base pairs and its sequence showed 99 % homology with the wild type strain. These mutations in UF16 could not be linked to phenotypic or genotypic changes on CoQ 10 biosynthetic pathway that resulted in improved yield. Hence, investigating the mutations responsible for deregulation of CoQ 10 pathway is essential to understand the cause of overproduction in UF16. Phylogenetic analysis based on RAPD bands and rRNA gene sequences coupled with morphological variations, exhibited the novelty of mutant UF16 having potential for improved CoQ 10 production.

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“…3,4) Living organisms possess different species of CoQ, and these are classified according to the length of the isoprenoid side chain. For example, human and S. pombe produce CoQ with ten isoprene units (CoQ 10 ), E. coli produces CoQ 8 , and Saccharomyces cerevisiae produces CoQ 6 . Side chain length is defined by polyprenyl diphosphate synthases.…”

mentioning

confidence: 99%

“…Production of CoQ 10 in fission yeast by expression of genes responsible for CoQ 10 Coenzyme Q (CoQ), also referred to as ubiquinone, is a component of the electron transport chain that participates in aerobic cellular respiration within eukaryotic mitochondria and, as such, is essential for ATP-dependent energy production. CoQ consists of a hydrophobic isoprenoid side chain and a quinone ring, and delivers electrons through the conversion of quinol (reduced form) to quinone (oxidized form).…”

mentioning

confidence: 99%

Production of CoQ10 in fission yeast by expression of genes responsible for CoQ10 biosynthesis

Moriyama

Hosono

Fujii

et al. 2015

Bioscience, Biotechnology, and Biochemistry

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Coenzyme Q10 (CoQ10) is essential for energy production and has become a popular supplement in recent years. In this study, CoQ10 productivity was improved in the fission yeast Schizosaccharomyces pombe. Ten CoQ biosynthetic genes were cloned and overexpressed in S. pombe. Strains expressing individual CoQ biosynthetic genes did not produce higher than a 10% increase in CoQ10 production. In addition, simultaneous expression of all ten coq genes did not result in yield improvements. Genes responsible for the biosynthesis of p-hydroxybenzoate and decaprenyl diphosphate, both of which are CoQ biosynthesis precursors, were also overexpressed. CoQ10 production was increased by overexpression of Eco_ubiC (encoding chorismate lyase), Eco_aroFFBR (encoding 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase), or Sce_thmgr1 (encoding truncated HMG-CoA reductase). Furthermore, simultaneous expression of these precursor genes resulted in two fold increases in CoQ10 production.

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Production of ubiquinone-10 using bacteria.

Cited by 103 publications

References 13 publications

Ubiquinone accumulation improves osmotic-stress tolerance in Escherichia coli

Ubiquinone accumulation improves osmotic-stress tolerance in Escherichia coli

Morphological and Molecular Differentiation of Sporidiobolus johnsonii ATCC 20490 and Its Coenzyme Q10 Overproducing Mutant Strain UF16

Production of CoQ10 in fission yeast by expression of genes responsible for CoQ10 biosynthesis

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