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A quantitative method for proteome reallocation using minimal regulatory interventions

Lastiri-Pancardo, Gustavo, Mercado-Hernandez, J.S, Kim, Juhyun, Jimenez, Jose and Utrilla, Jose (2019) A quantitative method for proteome reallocation using minimal regulatory interventions bioRxiv.

733592v1.full.pdf - Author's Original
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Engineering resource allocation in biological systems for synthetic biology applications is an ongoing challenge. Wild type organisms allocate abundant cellular resources for ensuring survival in changing environments, reducing the productivity of engineered functions. Here we present a novel approach for engineering the resource allocation of Escherichia coli by rationally modifying the transcriptional regulatory network of the bacterium. Our method (ReProMin) identifies the minimal set of genetic interventions that maximise the savings in cell resources that would normally be used to express non-essential genes. To this end we categorize Transcription Factors (TFs) according to the essentiality of the genes they regulate and we use available proteomic data to rank them based on its proteomic balance, defined as the net proteomic charge they release. Using a combinatorial approach, we design the removal of TFs that maximise the release of the proteomic charge and we validate the model predictions experimentally. Expression profiling of the resulting strain shows that our designed regulatory interventions are highly specific. We show that our resulting engineered strain containing only three mutations, theoretically releasing 0.5% of their proteome, has higher proteome budget and show increased production yield of a molecule of interest obtained from a recombinant metabolic pathway. This approach shows that combining whole-cell proteomic and regulatory data is an effective way of optimizing strains in a predictable way using conventional molecular methods.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Lastiri-Pancardo, Gustavo
Mercado-Hernandez, J.S
Utrilla, Jose
Date : 15 August 2019
Funders : UNAM–DGAPA-PAPIIT, Biology and Biotechnology Research Council (BBSRC)
DOI : 10.1101/733592
Grant Title : Biology and Biotechnology Research Council (BBSRC)
Copyright Disclaimer : CC-BY-NC-ND 4.0 International license (certified by peer review) is the author/funder. It is made available under The copyright holder for this preprint (which was not this version) posted August 15, 2019.
Projects : Newton Advanced Fellowship Project
Uncontrolled Keywords : Proteome minimization; Regulatory network; Escherichia coli; Rational design, Synthetic biology; Systems biology
Additional Information : The paper present in the repository is the version on bioRxiv. The version to be published has been accepted on 15/06/2020, and I will update the metadata when they send us the details of the published version.
Depositing User : James Marshall
Date Deposited : 16 Jun 2020 12:49
Last Modified : 16 Jun 2020 12:51

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