Metabolic engineering of Lactococcus lactis for high level accumulation of glutathione and S-adenosyl-l-methionine

  • Chutian Xu
  • Zhuwei Shi
  • Jiaqi Shao
  • Chengkai Yu
  • Zhinan XuEmail author
Original Paper


Glutathione (GSH) and S-adenosyl methionine (SAM) have been applied as liver-protective factors to prevent and treat many different liver damages and diseases. Due to their low stability and short half-life, oral administration of GSH or SAM might be replaced by continuous supplying through living lactic bacteria in yogurt. In this study, Lactococcus lactis was engineered via synthetic biology strategies to produce these two important molecules. The bi-functional GSH synthase gene (gshF) and SAM synthase gene (metK) were transformed into food-grade L. lactis together with an adhesion factor gene (cwaA). The highest accumulation of SAM (9.0 mg/L) and GSH (17.3 mg/L) was achieved after 17 h cultivation of the recombinant L. lactis. Meanwhile, the autoaggregation and hydrophobicity were also improved significantly, which suggested that this engineered L. lactis might have an increased colonization-prone ability in human GI. Our studies demonstrated one potential route to self-produce and deliver the liver-healthy factors within living probiotic bacteria.


Adhesion factor Glutathione Lactococcus lactis S-adenosylmethionine 



We thank much Prof. Haiqin Chen (College of Food Science and Technology, Jiangnan University, Wuxi, China) and Prof. Fei Liu (College of Medicine, Shandong University, Jinan, China) for the donation of the plasmid (pNZ8148), host strain (L. lactis NZ9000) and nisin product. We also thank much for the contribution by other H14Z1-Hangzhou iGEM members (JY Zhu, NT Qiu, K Zhou, JT Zhang, QY Shen, LX Li, JJ Wu, ML Kang) in our AP center, Mr. WZ Chen (College of Life and Marine Sciences, Shenzhen University, Shenzhen, China) as the group advisor and Ms. XM Tang (Chemistry teacher in AP center) as the group co-PI. Finally, we appreciate Zhejiang Vnor Environment Protection Corp. Ltd (Hangzhou, China) very much for financial supporting of our iGEM competition program.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethics approval

Ethics approval and consent to participate.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.AP CenterHangzhou No. 14 High SchoolHangzhouChina
  2. 2.Center for Synthetic Biology, College of Chemical and Biological EngineeringZhejiang UniversityHangzhouChina
  3. 3.Key Laboratory of Biomass Chemical Engineering (Education Ministry), College of Chemical and Biological EngineeringZhejiang UniversityHangzhouChina

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