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Enhanced synthesis of S-adenosyl-L-methionine through Combinatorial metabolic engineering and Bayesian optimization in Saccharomyces cerevisiae
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  • Wenhan Xiao ,
  • Xiangliu Shi ,
  • Haowei Huang,
  • Xiaogang Wang ,
  • Wenshu Liang ,
  • Xiaomei Zhang,
  • Guoqiang Xu,
  • Jianguo Xu,
  • Zhenghong Xu,
  • Jinsong Shi,
  • Fei Liu
Wenhan Xiao
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Xiangliu Shi
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Haowei Huang
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Xiaogang Wang
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Wenshu Liang
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Xiaomei Zhang
Jiangnan University
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Guoqiang Xu

Corresponding Author:[email protected]

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Jianguo Xu
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Zhenghong Xu
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Jinsong Shi
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S-Adenosyl-L-methionine (SAM) is a substrate for many enzyme-catalyzed reactions and provides methyl groups in numerous biological methylations, and thus has vast applications in the agriculture and medical field. Saccharomyces cerevisiae has been engineered as a platform with significant potential for producing SAM, although the current production has room for improvement. Thus, a method that consists of a series of metabolic engineering strategies was established this study. These strategies included enhancing SAM synthesis, increasing ATP supply, and down-regulating SAM metabolism and downregulating competing pathway. After combinatorial metabolic engineering, Bayesian optimization was conducted on the obtained strain C262P6 to optimize the fermentation medium. A final yield of 2972.8 mg/L at 36 h with 29.7% of the L-Met conversion rate in the shake flask was achieved, which was 26.3 times higher than that of its parent strain and the highest reported production in the shake flask to date. This paper establishes a feasible foundation for the construction of SAM-producing strains using metabolic engineering strategies and demonstrates the effectiveness of Bayesian optimization in optimizing fermentation medium to enhance the generation of SAM.
20 Nov 2023Submitted to Biotechnology Journal
24 Jan 20241st Revision Received
27 Jan 2024Assigned to Editor
27 Jan 2024Submission Checks Completed
27 Jan 2024Review(s) Completed, Editorial Evaluation Pending
27 Jan 2024Reviewer(s) Assigned
04 Feb 2024Editorial Decision: Revise Minor
10 Feb 2024Submission Checks Completed
10 Feb 2024Assigned to Editor
10 Feb 2024Review(s) Completed, Editorial Evaluation Pending