Heterologous and High Production of Ergothioneine in <i>Escherichia coli</i>

Osawa, Ryo; Kamide, Tomoyuki; Satoh, Yasuharu; Kawano, Yusuke; Ohtsu, Iwao; Dairi, Tohru

doi:10.1021/acs.jafc.7b04924

Cited by 43 publications

(48 citation statements)

References 15 publications

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“…Expression of egtBCDE genes from Mycobacterium smegmatis in Escherichia coli and optimisation of medium composition has led to 24 mg/l or 104 μM of secreted ERG (115) . The egtA gene from M. smegmatis was not expressed because E. coli contains a homologous glutamate-cysteine ligase encoded by gshA and involved in glutathione biosynthesis.…”

Section: Biosynthesis and Phylogenetic Distributionmentioning

confidence: 99%

The biology of ergothioneine, an antioxidant nutraceutical

et al. 2020

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Ergothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities. It is synthesised by a variety of microbes, especially fungi (including in mushroom fruiting bodies) and actinobacteria, but is not synthesised by plants and animals who acquire it via the soil and their diet, respectively. Animals have evolved a highly selective transporter for it, known as solute carrier family 22, member 4 (SLC22A4) in humans, signifying its importance, and ERG may even have the status of a vitamin. ERG accumulates differentially in various tissues, according to their expression of SLC22A4, favouring those such as erythrocytes that may be subject to oxidative stress. Mushroom or ERG consumption seems to provide significant prevention against oxidative stress in a large variety of systems. ERG seems to have strong cytoprotective status, and its concentration is lowered in a number of chronic inflammatory diseases. It has been passed as safe by regulatory agencies, and may have value as a nutraceutical and antioxidant more generally.

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Section: Biosynthesis and Phylogenetic Distributionmentioning

confidence: 99%

The biology of ergothioneine, an antioxidant nutraceutical

et al. 2020

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“…We recently succeeded in heterologous production of ERG in Escherichia coli utilizing ERG biosynthetic genes identified in Mycobacteria smegmatis. 8) In this study, we tried to produce ERG in a fungus with fungal biosynthetic genes. The biosynthetic pathway in Neurospora crassa was recently reported (Figure 1).…”

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confidence: 99%

Ergothioneine production with Aspergillus oryzae

Takusagawa

Satoh

Ohtsu

et al. 2019

Bioscience, Biotechnology, and Biochemistry

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Ergothioneine production with Aspergillus oryzae To establish a reliable and practical ergothioneine (ERG) supply, we employed fermentative ERG production using Aspergillus oryzae, a fungus used for food production. We heterologously overexpressed the egt-1 and-2 genes of Neurospora crassa in A. oryzae and succeeded in producing ERG (231.0 mg/kg of media, which was 20 times higher than the wild type).

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“…While metabolic engineering of the nitrogen metabolism in yeast can lead to unexpected results, because it is so tightly regulated, engineering the strain for higher production of individual amino acids pools could lead to higher ERG titers. This is similar to the approach taken in E. coli , where use was made of a strain that was already overproducing cysteine (Osawa et al, 2018). In yeast, it is also possible to adopt several strategies that increase the amount of available SAM and/or methionine (Chen et al, 2016) to potentially improve ergothioneine production.…”

Section: Discussionmentioning

confidence: 97%

“…Production of ergothioneine in microbial cell factories would provide a sustainable low-cost alternative to its current manufacturing processes. So far, fermentative ERG production has been reported in bacteria and filamentous fungi, including Methylobacterium aquaticum strain 22A (Alamgir et al, 2015), Aureobasidium pullulans (Fujitani et al, 2018), Rhodotorula mucilaginosa (Fujitani et al, 2018) , cyanobacteria (Pfeiffer et al, 2011), Aspergillus oryzae (Takusagawa et al, 2019) and Escherichia coli (Osawa et al, 2018; Tanaka et al, 2019). To the best of our knowledge, there are no reports on ergothioneine production in baker’s yeast, which is the preferred host for the production of nutraceuticals (Huang et al, 2008; Li and Borodina, 2014; Yuan and Alper, 2019).…”

Section: Introductionmentioning

confidence: 99%

Engineering the yeastSaccharomyces cerevisiaefor the production of L-(+)-ergothioneine

Hoek

Darbani

Zugaj

et al. 2019

Preprint

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20 cerevisiae, yeast, nutraceutical 21 22 Abbreviations: ERG L-(+)-ergothioneine, HCO S-(hercyn-2-yl)-L-cysteine S-oxide, PBS 23 phosphate-buffered saline, PI propidium iodide, PLP pyridoxal 5'-phosphate, SAM S-adenosyl-24 L-methionine 25 26Abstract 27 L-(+)-Ergothioneine is an unusual, naturally occurring antioxidant nutraceutical that has been 28 shown to help reduce cellular oxidative damage. Humans do not biosynthesise it, so can acquire 29 it only from their diet; it exploits a specific transporter (SLC22A4) for its uptake. ERG is 30 considered to be a nutraceutical and possible vitamin that is involved in the maintenance of 31 health, and seems to be at too low a concentration in several diseases in vivo. Ergothioneine is 32 thus a potentially useful dietary supplement. Present methods of commercial production rely on 33 extraction from natural sources or on chemical synthesis. Here we describe the engineering of 34 the baker's yeast Saccharomyces cerevisiae to produce ergothioneine by fermentation in defined 35 media. After integrating combinations of ERG biosynthetic pathways from different organisms, 36 we screened yeast strains for their production of ERG. The highest-producing strain was also 37 engineered with known ergothioneine transporters. The effect of amino acid supplementation of 38 the medium was investigated and the nitrogen metabolism of S. cerevisiae was altered by knock-39 out of TOR1 or YIH1. We also optimized the media composition using fractional factorial 40 methods. Our optimal strategy led to a titer of 598 ± 18 mg/L ergothioneine in fed-batch culture 41 in bioreactors. Because S. cerevisiae is a GRAS ('generally recognised as safe') organism that is 42 2 widely used for nutraceutical production, this work provides a promising process for the 43 biosynthetic production of ERG. 44 45

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Heterologous and High Production of Ergothioneine in Escherichia coli

Cited by 43 publications

References 15 publications

The biology of ergothioneine, an antioxidant nutraceutical

The biology of ergothioneine, an antioxidant nutraceutical

Ergothioneine production with Aspergillus oryzae

Engineering the yeastSaccharomyces cerevisiaefor the production of L-(+)-ergothioneine

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