Identification of bottlenecks in Escherichia coli engineered for the production of CoQ10

Cluis, Corinne P.; Ekins, Andrew; Narcross, Lauren; Jiang, Heng; Gold, Nicholas D.; Burja, Adam M.; Martin, Vincent J. J.

doi:10.1016/j.ymben.2011.09.009

Cited by 49 publications

(44 citation statements)

References 75 publications

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“…The novelty of the proposed pathway is the use of PHB from the ubiquinone pathway as an intermediate for the production of MA. In the ubiquinone pathway, the second enzymatic step that converts PHB to 3-octaprenyl-4-hydoxybenzoate is the rate-limiting step (21). Hence, production of MA using the proposed pathway is benefitted by utilizing almost all the PHB.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Engineering of a Novel Muconic Acid Biosynthesis Pathway via 4-Hydroxybenzoic Acid in Escherichia coli

Sengupta

Jonnalagadda

Goonewardena

et al. 2015

Appl Environ Microbiol

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cis,cis-Muconic acid (MA) is a commercially important raw material used in pharmaceuticals, functional resins, and agrochemicals. MA is also a potential platform chemical for the production of adipic acid (AA), terephthalic acid, caprolactam, and 1,6-hexanediol. A strain of Escherichia coli K-12, BW25113, was genetically modified, and a novel nonnative metabolic pathway was introduced for the synthesis of MA from glucose. The proposed pathway converted chorismate from the aromatic amino acid pathway to MA via 4-hydroxybenzoic acid (PHB). Three nonnative genes, pobA, aroY, and catA, coding for 4-hydroxybenzoate hydrolyase, protocatechuate decarboxylase, and catechol 1,2-dioxygenase, respectively, were functionally expressed in E. coli to establish the MA biosynthetic pathway. E. coli native genes ubiC, aroF FBR , aroE, and aroL were overexpressed and the genes ptsH, ptsI, crr, and pykF were deleted from the E. coli genome in order to increase the precursors of the proposed MA pathway. The final engineered E. coli strain produced nearly 170 mg/liter of MA from simple carbon sources in shake flask experiments. The proposed pathway was proved to be functionally active, and the strategy can be used for future metabolic engineering efforts for production of MA from renewable sugars.

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Section: Discussionmentioning

confidence: 99%

Metabolic Engineering of a Novel Muconic Acid Biosynthesis Pathway via 4-Hydroxybenzoic Acid in Escherichia coli

Sengupta

Jonnalagadda

Goonewardena

et al. 2015

Appl Environ Microbiol

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“…Chorismate pyruvate lyase (UbiC) catalyzes the first committed step in the biosynthesis of ubiquinone, which converts chorismate to 4-hydroxybenzoate (Cluis et al 2007(Cluis et al , 2011.…”

Section: Increasing the Supply Of 4-hydroxybenzoate For Phenol Producmentioning

confidence: 99%

Construction of a novel phenol synthetic pathway in Escherichia coli through 4-hydroxybenzoate decarboxylation

Miao

Diao

et al. 2015

Appl Microbiol Biotechnol

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Phenol is a bulk chemical with lots of applications in the chemical industry. Fermentative production of phenol had been realized in both Pseudomonas putida and Escherichia coli by recruiting tyrosine phenol-lyase (TPL). The TPL pathway needs tyrosine as the direct precursor for phenol production. In this work, a novel phenol synthetic pathway was created in E. coli by recruiting 4-hydroxybenzoate decarboxylase, which can convert 4-hydroxybenzoate to phenol and carbon dioxide. Activating 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthase and chorismate pyruvate lyase (UbiC) through plasmid overexpression led to 7- and 69-fold increase of phenol production, respectively, demonstrating that these two enzymes were the rate-limiting steps for phenol production. Genetically stable strains were then obtained by gene integration and gene modulation directly in chromosome. Phenol titer increased 147-fold (from 1.7 to 250 mg/L) after modulating the DAHP synthase, UbiC, and 4-hydroxybenzoate decarboxylase genes in chromosome. Five solvents were tested for two-phase extractive fermentation to eliminate phenol toxicity to E. coli cells. Tributyrin and dibutyl phthalate were the best two solvents for improving phenol production, leading to 23 and 30 % increase of total phenol production, respectively. Two-phase fed-batch fermentation of the best strain Phe009 was performed in a 7 L fermentor, which produced 9.51 g/L phenol with a yield of 0.061 g/g glucose.

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“…Individual overexpression of these genes led to improved production of CoQ, and simultaneous coexpression yielded further gains. These genes were previously reported to improve CoQ productivity in E. coli (Eco_aroF FBR and Eco_ubiC) 29,30) and S. pombe (HMG-CoA reductase from S. pombe) 31) . Eco_aroF FBR and Eco_ubiC were previously examined only in E. coli, and this is the first report of their effectiveness in fission yeast.…”

Section: Discussionmentioning

confidence: 96%

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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Identification of bottlenecks in Escherichia coli engineered for the production of CoQ10

Cited by 49 publications

References 75 publications

Metabolic Engineering of a Novel Muconic Acid Biosynthesis Pathway via 4-Hydroxybenzoic Acid in Escherichia coli

Metabolic Engineering of a Novel Muconic Acid Biosynthesis Pathway via 4-Hydroxybenzoic Acid in Escherichia coli

Construction of a novel phenol synthetic pathway in Escherichia coli through 4-hydroxybenzoate decarboxylation

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

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