Ergothioneine production through metabolic engineering

An ergothioneine and gene technology, applied in the field of ergothioneine production through metabolic engineering, can solve the problems that EgtE enzyme cannot be overexpressed, EgtB activity is low, and production is limited.

Active Publication Date: 2015-08-19
刘平华 +2
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Problems solved by technology

However, there are three major obstacles hindering the use of currently known ergothioneine biosynthetic pathways produced by fermentation: (1) the EgtE enzyme cannot be overexpressed; (2) the activity of EgtB is low; (3) ergothioneine and glutathione Potential competition between glycides for y-Glu-Cys would limit yield

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  • Ergothioneine production through metabolic engineering
  • Ergothioneine production through metabolic engineering
  • Ergothioneine production through metabolic engineering

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example 1

[0307] Example 1: Production of Ergothioneine by Metabolic Engineering (In Vitro Enzymatic Means)

[0308] Identification of a gene cluster for ergothioneine biosynthesis. Ergothioneine and ovothiol (5&7, figure 1 ) are metabolites of two thiol-imidazoles isolated from ergot by Tanret in 1909 [1]. The presence of ergothioneine-specific transporters in humans [2] allows us to enrich ergothioneine from the diet, reaching millimolar concentrations in several organs such as the liver, kidney, central nervous system and erythrocytes[ 3]. Unlike other thiols, the balance between the thiolate and thione forms of the thiol-imidazole side chain in ergothioneine and ovothiol is predominantly in favor of the thione form (e.g. figure 1 5) in [3f, 4], which makes them more stable in oxidation than other thiol mimics (eg, glutathione) [4a]. This unique redox property of ergothioneine [4a, 5] enables it to protect hemoglobin from oxidation in erythrocytes and avoid cataract formation in ...

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Abstract

The present disclosure relates to the production of ergothioneine through either in vitro enzymatic transformations or fermentations using microbials created by metabolic engineering. Also disclosed are transformed cells useful in such methods and ergothioneine produced by such methods. Transformed cells of the disclosure are capable of converting histidine and cysteine or hercynine and cysteine into ergothioneine in greater efficiency than the untransformed wild-type cells.

Description

[0001] related application [0002] This application claims priority and the benefit of US Patent Provisional Application No. 61 / 740,829, filed December 21, 2012. The entire content of this application is incorporated herein by reference in its entirety. [0003] Government funding [0004] This invention was made under government grant GM093903 awarded by the National Institutes of Health and CHE-0748504 awarded by the National Science Foundation. The US Government has certain rights in this invention. technical field [0005] The present disclosure generally relates to the production of ergothioneine by cell-free enzymatic conversion or by fermentation using microorganisms produced by metabolic engineering. Background technique [0006] Ergothioneine is an amino acid containing a thiol group isolated from ergot by Tanret in 1909. Its unique redox properties make it one of the best natural antioxidants. Furthermore, since it is specifically enriched from food by many h...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P13/04C12N15/52C12N15/70
CPCC12P13/04C12N15/52C07D233/42C12P17/10
Inventor 刘平华宋恒胡文
Owner 刘平华
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