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Holistic engineering of cell-free systems through proteome-reprogramming synthetic circuits.
Nat Commun. 2020 Jun 19; 11(1):3138.NC

Abstract

Synthetic biology has focused on engineering genetic modules that operate orthogonally from the host cells. A synthetic biological module, however, can be designed to reprogram the host proteome, which in turn enhances the function of the synthetic module. Here, we apply this holistic synthetic biology concept to the engineering of cell-free systems by exploiting the crosstalk between metabolic networks in cells, leading to a protein environment more favorable for protein synthesis. Specifically, we show that local modules expressing translation machinery can reprogram the bacterial proteome, changing the expression levels of more than 700 proteins. The resultant feedback generates a cell-free system that can synthesize fluorescent reporters, protein nanocages, and the gene-editing nuclease Cas9, with up to 5-fold higher expression level than classical cell-free systems. Our work demonstrates a holistic approach that integrates synthetic and systems biology concepts to achieve outcomes not possible by only local, orthogonal circuits.

Authors+Show Affiliations

Department of Biomedical Engineering, University of California, Davis, Davis, CA, 95616, USA.Department of Biomedical Engineering, University of California, Davis, Davis, CA, 95616, USA.Department of Biomedical Engineering, University of California, Davis, Davis, CA, 95616, USA.School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, Block N1.3, Singapore, 637457, Singapore.School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, Block N1.3, Singapore, 637457, Singapore.Department of Chemical Engineering, University of California, Davis, Davis, CA, 95616, USA.Department of Biomedical Engineering, University of California, Davis, Davis, CA, 95616, USA. cmtan@ucdavis.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32561745

Citation

Contreras-Llano, Luis E., et al. "Holistic Engineering of Cell-free Systems Through Proteome-reprogramming Synthetic Circuits." Nature Communications, vol. 11, no. 1, 2020, p. 3138.
Contreras-Llano LE, Meyer C, Liu Y, et al. Holistic engineering of cell-free systems through proteome-reprogramming synthetic circuits. Nat Commun. 2020;11(1):3138.
Contreras-Llano, L. E., Meyer, C., Liu, Y., Sarker, M., Lim, S., Longo, M. L., & Tan, C. (2020). Holistic engineering of cell-free systems through proteome-reprogramming synthetic circuits. Nature Communications, 11(1), 3138. https://doi.org/10.1038/s41467-020-16900-7
Contreras-Llano LE, et al. Holistic Engineering of Cell-free Systems Through Proteome-reprogramming Synthetic Circuits. Nat Commun. 2020 Jun 19;11(1):3138. PubMed PMID: 32561745.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Holistic engineering of cell-free systems through proteome-reprogramming synthetic circuits. AU - Contreras-Llano,Luis E, AU - Meyer,Conary, AU - Liu,Yao, AU - Sarker,Mridul, AU - Lim,Sierin, AU - Longo,Marjorie L, AU - Tan,Cheemeng, Y1 - 2020/06/19/ PY - 2020/03/05/received PY - 2020/05/27/accepted PY - 2020/6/21/entrez PY - 2020/6/21/pubmed PY - 2020/6/21/medline SP - 3138 EP - 3138 JF - Nature communications JO - Nat Commun VL - 11 IS - 1 N2 - Synthetic biology has focused on engineering genetic modules that operate orthogonally from the host cells. A synthetic biological module, however, can be designed to reprogram the host proteome, which in turn enhances the function of the synthetic module. Here, we apply this holistic synthetic biology concept to the engineering of cell-free systems by exploiting the crosstalk between metabolic networks in cells, leading to a protein environment more favorable for protein synthesis. Specifically, we show that local modules expressing translation machinery can reprogram the bacterial proteome, changing the expression levels of more than 700 proteins. The resultant feedback generates a cell-free system that can synthesize fluorescent reporters, protein nanocages, and the gene-editing nuclease Cas9, with up to 5-fold higher expression level than classical cell-free systems. Our work demonstrates a holistic approach that integrates synthetic and systems biology concepts to achieve outcomes not possible by only local, orthogonal circuits. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/32561745/Holistic_engineering_of_cell-free_systems_through_proteome-reprogramming_synthetic_circuits L2 - http://dx.doi.org/10.1038/s41467-020-16900-7 DB - PRIME DP - Unbound Medicine ER -
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