ATP dynamic regeneration strategy for enhancing co-production of glutathione and S-adenosylmethionine in Escherichia col
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ORIGINAL RESEARCH PAPER
ATP dynamic regeneration strategy for enhancing coproduction of glutathione and S-adenosylmethionine in Escherichia coli Ya Wei Chen . Yuan Liao . Wei Zhen Kong . Shu Han Wang
Received: 7 May 2020 / Accepted: 13 August 2020 Ó Springer Nature B.V. 2020
Abstract Objectives In general, a sufficient supply of ATP can promote the synthesis of ATP-driven metabolites, but excessive ATP will lead to the inhibition of cell growth. For enhancing the co-production of glutathione(GSH) and S-adenosylmethionine(SAM), a dynamic ATP regeneration strategy was developed. Results The novel ATP regeneration strategy consisting of ATP-sensing riboswitch ydaO motif, polyphosphate kinase (PPK), and Vitreoscilla hemoglobin (VHb) was successfully applied in Escherichia coli. The intracellular ATP level was always around 0.60 mg/g dry cell weight during the fermentation process, resulting in significantly enhanced co-production of GSH and SAM. The GSH titer and SAM titer in the strain CGS-2 increased by 137.40% and 82.18% after fermentation for 24 h, compared with the control strain. Conclusions The ATP regulation strategy is expected to be a favorable tool to improve the
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10529-020-02989-9) contains supplementary material, which is available to authorized users. Y. W. Chen (&) Y. Liao W. Z. Kong S. H. Wang College of Chemical and Pharmaceutical Engineering, Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang 471023, People’s Republic of China e-mail: [email protected]
efficiency of microbial cell factories. The proposed ATP dynamic regeneration approach may be applicable for cost-effective, high-yield production of ATPdriven metabolites. Keywords ATP Glutathione Sadenosylmethionine Regeneration Regulation Riboswitch
Introduction Glutathione (GSH) and S-adenosylmethionine (SAM) are of commercial interest as research reagents, pharmaceuticals, dietary supplements, and cosmetic additives. Therefore, attempts have been made to achieve GSH and SAM production by fermentation utilizing various types of microorganisms in recent years (Kobayashi et al. 2019). GSH and SAM are produced by ATP-consuming reactions. Besides, they are both involved in the thiol metabolism of cells. Therefore, they can be produced simultaneously by fermentation due to their tightly interrelated metabolic pathways(Brosnan et al. 2007). According to the research, related amino acids and ATP are limiting precursors in the GSH and SAM biosynthesis (Li et al. 2017). Since it is not cost-effective to add ATP directly to the medium, a sufficient supply of ATP as a precursor and energy carrier become critical to the GSH and SAM accumulation (Li et al. 2017). The
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scholars have made many attempts for enhancing the ATP supply, such as the addition of energy substrates, controlling fermentation process, or genetic manipulation (Hara and Kondo 2015). Howe
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