Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Bioengineering of Escherichia coli Nissle 1917 for Overproduction and Excretion of Spermidine, a Key Metabolite in Human Health

Version 1 : Received: 14 October 2022 / Approved: 17 October 2022 / Online: 17 October 2022 (12:09:41 CEST)

A peer-reviewed article of this Preprint also exists.

Caffaratti, C.; Plazy, C.; Cunin, V.; Toussaint, B.; Le Gouellec, A. Bioengineering of Escherichia coli Nissle 1917 for Production and Excretion of Spermidine, a Key Metabolite in Human Health. Metabolites 2022, 12, 1061. Caffaratti, C.; Plazy, C.; Cunin, V.; Toussaint, B.; Le Gouellec, A. Bioengineering of Escherichia coli Nissle 1917 for Production and Excretion of Spermidine, a Key Metabolite in Human Health. Metabolites 2022, 12, 1061.

Abstract

Over the past decade, studies have demonstrated the importance of bioactive metabolites derived from the microbiota in the regulation of physiological processes essential for homeostasis and the maintenance of human health. Strategies to modulate the production of these metabolites in the gastrointestinal tract hold promise for combating dysbiosis or inflammatory bowel disease. Metabolic engineering of probiotics could be one of these solutions. In this work, we engineered Escherichia coli Nissle 1917 (EcN) to overproduce spermidine, a metabolite known for its anti-immunosenescence and anti-inflammatory properties. Using a rational synthetic biology approach coupled with analysis by high resolution mass spectrometry, we designed in several steps and validated engineered probiotics overproducing and excreting spermidine. Based on our results, we first added the enzyme substrate putrescine and showed the overproduction of spermidine and decided to add a transporter limiting the production of the acetylated form of spermidine. Next, we used untargeted metabolomics to study the impact of engineering on the central metabolism of E. coli Nissle. Untargeted metabolomics appears to be a good strategy to optimize the metabolic engineering of probiotic strains and thus accelerate their development for personalized medicine.

Keywords

Microbiota; Immunity; Spermidine; Metabolic engineering; Probiotics; Live Biotherapeutic Product; Metabolomics

Subject

Biology and Life Sciences, Biology and Biotechnology

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.