4.8 Article

Reversible thermal regulation for bifunctional dynamic control of gene expression in Escherichia coli

Journal

NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -

Publisher

NATURE RESEARCH
DOI: 10.1038/s41467-021-21654-x

Keywords

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Funding

  1. Ministry of Science and Technology of China [2018YFA0900200, 2016YFB0302500]
  2. National Natural Science Foundation of China [21761132013, 31870859, 32001029, 31961133017, 31961133018, 31961133019]
  3. Tsinghua University-INDITEX Sustainable Development Fund [TISD201907]
  4. NSFC
  5. EU H2020 collaboration
  6. European Union [870294]

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The researchers designed a thermosensitive switch for spatial and temporal control of colony pattern, cell shape and polymer production.
Genetically programmed circuits allowing bifunctional dynamic regulation of enzyme expression have far-reaching significances for various bio-manufactural purposes. However, building a bio-switch with a post log-phase response and reversibility during scale-up bioprocesses is still a challenge in metabolic engineering due to the lack of robustness. Here, we report a robust thermosensitive bio-switch that enables stringent bidirectional control of gene expression over time and levels in living cells. Based on the bio-switch, we obtain tree ring-like colonies with spatially distributed patterns and transformer cells shifting among spherical-, rod- and fiber-shapes of the engineered Escherichia coli. Moreover, fed-batch fermentations of recombinant E. coli are conducted to obtain ordered assembly of tailor-made biopolymers polyhydroxyalkanoates including diblock- and random-copolymer, composed of 3-hydroxybutyrate and 4-hydroxybutyrate with controllable monomer molar fraction. This study demonstrates the possibility of well-organized, chemosynthesis-like block polymerization on a molecular scale by reprogrammed microbes, exemplifying the versatility of thermo-response control for various practical uses. Genetic circuits can be built with bifunctional dynamic regulation of gene expression. Here the authors design a thermosensitive switch for spatial and temporal control of colony pattern, cell shape and polymer production.

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