Gram-scale fermentative production of ergothioneine driven by overproduction of cysteine in Escherichia coli.

Abstract:

:Ergothioneine (ERG), a unique thiol compound, is suggested to function as an antioxidant and cytoprotectant. Despite several recent attempts to produce ERG using various organisms, its yield was still very low and the costs remained high. Since the level of ERG produced depends strictly on the availability of three distinct precursor amino acids (L-cysteine (Cys), L-histidine, and L-methionine (Met)), metabolic engineering for enhancement of the flux toward ERG biosynthesis is required. Herein, we took advantage of a high-Cys production system using Escherichia coli cells, in which Cys biosynthesis and excretion were activated, and applied it to the fermentative production of ERG from glucose. The Cys overproduction in E. coli cells carrying the egtBCDE genes from Mycobacterium smegmatis was effective for ERG production. Furthermore, coexpression of the egtA gene, which encodes γ-glutamylcysteine synthetase that synthesizes the γ-glutamylcysteine used as a sulfur source of ERG biosynthesis, enhanced ERG production even though E. coli intrinsically has γ-glutamylcysteine synthetase. Additionally, disruption of the metJ gene that encodes the transcriptional repressor involved in Met metabolism was effective in further increasing the production of ERG. Finally, we succeeded in the high-level production of 1.31 g/L ERG in a fed-batch culture process using a jar fermenter.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Tanaka N,Kawano Y,Satoh Y,Dairi T,Ohtsu I

doi

10.1038/s41598-018-38382-w

subject

Has Abstract

pub_date

2019-02-13 00:00:00

pages

1895

issue

1

issn

2045-2322

pii

10.1038/s41598-018-38382-w

journal_volume

9

pub_type

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