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A multilayered biocontainment system for laboratory and probiotic yeast

Titelangaben

Maneira, Carla ; Becker, Sina ; Chamas, Alexandre ; Lackner, Gerald:
A multilayered biocontainment system for laboratory and probiotic yeast.
In: Metabolic Engineering. (2025) Heft 91 . - S. 442-454.
ISSN 1096-7184
DOI: https://doi.org/10.1016/j.ymben.2025.06.009

Volltext

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Abstract

The containment of genetically engineered microorganisms to designated environments of action is a paramount step in preventing their spread to nature. Physical barriers were traditionally employed to solve this issue, nevertheless, the growing number of biotechnological operations in open dynamic environments calls for intrinsic biocontainment. Here we describe the development of genetically embedded safeguard systems for both a laboratory strain of Saccharomyces cerevisiae and the commercial probiotic Saccharomyces cerevisiae var. boulardii. In a stepwise approach, single-input metabolic circuits based either on a synthetic auxotrophy or a CRISPR-based kill switch were developed before their combination into an orthogonal two-input system. All circuits are based on gut-active molecules or environmental cues, making them amenable to microbiome therapy applications. The final two-input system is stable for more than a hundred generations while achieving less than one escapee in 109 CFUs after incubation under restrictive conditions for at least six days. Biocontained strains can robustly produce heterologous proteins under permissive conditions, supporting their future use in the most varied applications, like in-situ production and delivery of pharmaceutically active metabolites.

Weitere Angaben

Publikationsform: Artikel in einer Zeitschrift
Begutachteter Beitrag: Ja
Keywords: biocontainment system; probiotic yeast; genetically engineered microorganisms; Saccharomyces cerevisia
Institutionen der Universität: Fakultäten > Fakultät für Lebenswissenschaften: Lebensmittel, Ernährung und Gesundheit > Lehrstuhl Biochemie der Mikroorganismen > Lehrstuhl Biochemie der Mikroorganismen - Univ.-Prof. Dr. Gerald Lackner
Titel an der UBT entstanden: Ja
Themengebiete aus DDC: 500 Naturwissenschaften und Mathematik > 500 Naturwissenschaften
500 Naturwissenschaften und Mathematik > 570 Biowissenschaften; Biologie
600 Technik, Medizin, angewandte Wissenschaften
600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
Eingestellt am: 08 Jul 2025 06:49
Letzte Änderung: 08 Jul 2025 06:49
URI: https://eref.uni-bayreuth.de/id/eprint/94037