A genetic toolbox to empower Paracoccus pantotrophus DSM 2944 as a metabolically versatile SynBio chassis.

Adaptive laboratory evolution Bioeconomy Genetic toolbox Metabolic engineering Paracoccus Plastics SynBio chassis

Journal

Microbial cell factories
ISSN: 1475-2859
Titre abrégé: Microb Cell Fact
Pays: England
ID NLM: 101139812

Informations de publication

Date de publication:
15 Feb 2024
Historique:
received: 12 01 2024
accepted: 05 02 2024
medline: 16 2 2024
pubmed: 16 2 2024
entrez: 15 2 2024
Statut: epublish

Résumé

To contribute to the discovery of new microbial strains with metabolic and physiological robustness and develop them into successful chasses, Paracoccus pantotrophus DSM 2944, a Gram-negative bacterium from the phylum Alphaproteobacteria and the family Rhodobacteraceae, was chosen. The strain possesses an innate ability to tolerate high salt concentrations. It utilizes diverse substrates, including cheap and renewable feedstocks, such as C1 and C2 compounds. Also, it can consume short-chain alkanes, predominately found in hydrocarbon-rich environments, making it a potential bioremediation agent. The demonstrated metabolic versatility, coupled with the synthesis of the biodegradable polymer polyhydroxyalkanoate, positions this microbial strain as a noteworthy candidate for advancing the principles of a circular bioeconomy. The study aims to follow the chassis roadmap, as depicted by Calero and Nikel, and de Lorenzo, to transform wild-type P. pantotrophus DSM 2944 into a proficient SynBio (Synthetic Biology) chassis. The initial findings highlight the antibiotic resistance profile of this prospective SynBio chassis. Subsequently, the best origin of replication (ori) was identified as RK2. In contrast, the non-replicative ori R6K was selected for the development of a suicide plasmid necessary for genome integration or gene deletion. Moreover, when assessing the most effective method for gene transfer, it was observed that conjugation had superior efficiency compared to electroporation, while transformation by heat shock was ineffective. Robust host fitness was demonstrated by stable plasmid maintenance, while standardized gene expression using an array of synthetic promoters could be shown. pEMG-based scarless gene deletion was successfully adapted, allowing gene deletion and integration. The successful integration of a gene cassette for terephthalic acid degradation is showcased. The resulting strain can grow on both monomers of polyethylene terephthalate (PET), with an increased growth rate achieved through adaptive laboratory evolution. The chassis roadmap for the development of P. pantotrophus DSM 2944 into a proficient SynBio chassis was implemented. The presented genetic toolkit allows genome editing and therewith the possibility to exploit Paracoccus for a myriad of applications.

Sections du résumé

BACKGROUND BACKGROUND
To contribute to the discovery of new microbial strains with metabolic and physiological robustness and develop them into successful chasses, Paracoccus pantotrophus DSM 2944, a Gram-negative bacterium from the phylum Alphaproteobacteria and the family Rhodobacteraceae, was chosen. The strain possesses an innate ability to tolerate high salt concentrations. It utilizes diverse substrates, including cheap and renewable feedstocks, such as C1 and C2 compounds. Also, it can consume short-chain alkanes, predominately found in hydrocarbon-rich environments, making it a potential bioremediation agent. The demonstrated metabolic versatility, coupled with the synthesis of the biodegradable polymer polyhydroxyalkanoate, positions this microbial strain as a noteworthy candidate for advancing the principles of a circular bioeconomy.
RESULTS RESULTS
The study aims to follow the chassis roadmap, as depicted by Calero and Nikel, and de Lorenzo, to transform wild-type P. pantotrophus DSM 2944 into a proficient SynBio (Synthetic Biology) chassis. The initial findings highlight the antibiotic resistance profile of this prospective SynBio chassis. Subsequently, the best origin of replication (ori) was identified as RK2. In contrast, the non-replicative ori R6K was selected for the development of a suicide plasmid necessary for genome integration or gene deletion. Moreover, when assessing the most effective method for gene transfer, it was observed that conjugation had superior efficiency compared to electroporation, while transformation by heat shock was ineffective. Robust host fitness was demonstrated by stable plasmid maintenance, while standardized gene expression using an array of synthetic promoters could be shown. pEMG-based scarless gene deletion was successfully adapted, allowing gene deletion and integration. The successful integration of a gene cassette for terephthalic acid degradation is showcased. The resulting strain can grow on both monomers of polyethylene terephthalate (PET), with an increased growth rate achieved through adaptive laboratory evolution.
CONCLUSION CONCLUSIONS
The chassis roadmap for the development of P. pantotrophus DSM 2944 into a proficient SynBio chassis was implemented. The presented genetic toolkit allows genome editing and therewith the possibility to exploit Paracoccus for a myriad of applications.

Identifiants

pubmed: 38360576
doi: 10.1186/s12934-024-02325-0
pii: 10.1186/s12934-024-02325-0
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

53

Subventions

Organisme : Federal Ministry of Education and Research (BMBF, Germany)
ID : FKZ 031B0854
Organisme : Federal Ministry of Education and Research (BMBF, Germany)
ID : FKZ 031B0854
Organisme : Federal Ministry of Education and Research (BMBF, Germany)
ID : FKZ 031B0854
Organisme : Federal Ministry of Education and Research (BMBF, Germany)
ID : FKZ 031B0854
Organisme : Federal Ministry of Education and Research (BMBF, Germany)
ID : FKZ 031B0854
Organisme : Federal Ministry of Education and Research (BMBF, Germany)
ID : FKZ 031B0854
Organisme : Deutsche Forschungsgemeinschaft (DFG: German Research Foundation)
ID : FSC 2186

Informations de copyright

© 2024. The Author(s).

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Auteurs

Upasana Pal (U)

Institute of Applied Microbiology, RWTH Aachen University, Aachen, Germany.

Denise Bachmann (D)

Institute of Applied Microbiology, RWTH Aachen University, Aachen, Germany.

Chiara Pelzer (C)

Institute of Applied Microbiology, RWTH Aachen University, Aachen, Germany.

Julia Christiansen (J)

Institute of Applied Microbiology, RWTH Aachen University, Aachen, Germany.
Chair of Microbiology, Technical University of Munich, Freising, Germany.

Lars M Blank (LM)

Institute of Applied Microbiology, RWTH Aachen University, Aachen, Germany.

Till Tiso (T)

Institute of Applied Microbiology, RWTH Aachen University, Aachen, Germany. till.tiso@rwth-aachen.de.

Classifications MeSH