Probing the operability regime of an engineered ribocomputing unit in terms of dynamic range maintenance with extracellular changes and time.

Biological computation Regulatory RNA Synthetic biology Systems biology

Journal

Journal of biological engineering
ISSN: 1754-1611
Titre abrégé: J Biol Eng
Pays: England
ID NLM: 101306640

Informations de publication

Date de publication:
2020
Historique:
received: 07 11 2019
accepted: 10 03 2020
entrez: 1 4 2020
pubmed: 1 4 2020
medline: 1 4 2020
Statut: epublish

Résumé

Synthetic biology aims at engineering gene regulatory circuits to end with cells (re)programmed on purpose to implement novel functions or discover natural behaviors. However, one overlooked question is whether the resulting circuits perform as intended in variety of environments or with time. Here, we considered a recently engineered genetic system that allows programming the cell to work as a minimal computer (arithmetic logic unit) in order to analyze its operability regime. This system involves transcriptional and post-transcriptional regulations. In particular, we studied the analog behavior of the system, the effect of physicochemical changes in the environment, the impact on cell growth rate of the heterologous expression, and the ability to maintain the arithmetic functioning over time. Conclusively, our results suggest 1) that there are wide input concentration ranges that the system can correctly process, the resulting outputs being predictable with a simple mathematical model, 2) that the engineered circuitry is quite sensitive to temperature effects, 3) that the expression of heterologous small RNAs is costly for the cell, not only of heterologous proteins, and 4) that a proper genetic reorganization of the system to reduce the amount of heterologous DNA in the cell can improve its evolutionary stability.

Identifiants

pubmed: 32226483
doi: 10.1186/s13036-020-00234-5
pii: 234
pmc: PMC7098154
doi:

Types de publication

Journal Article

Langues

eng

Pagination

12

Informations de copyright

© The Author(s) 2020.

Déclaration de conflit d'intérêts

Competing interestsThe authors declare that they have no competing interests.

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Auteurs

Roser Montagud-Martínez (R)

1Institute for Integrative Systems Biology (I2SysBio), CSIC - University of Valencia, 46980 Paterna, Valencia Spain.

Jordi Ventura (J)

1Institute for Integrative Systems Biology (I2SysBio), CSIC - University of Valencia, 46980 Paterna, Valencia Spain.

Rafael Ballesteros-Garrido (R)

1Institute for Integrative Systems Biology (I2SysBio), CSIC - University of Valencia, 46980 Paterna, Valencia Spain.
2Present address: Department of Organic Chemistry, University of Valencia, 46100 Burjassot, Valencia Spain.

Arantxa Rosado (A)

1Institute for Integrative Systems Biology (I2SysBio), CSIC - University of Valencia, 46980 Paterna, Valencia Spain.

Guillermo Rodrigo (G)

1Institute for Integrative Systems Biology (I2SysBio), CSIC - University of Valencia, 46980 Paterna, Valencia Spain.

Classifications MeSH