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Pyruvate-responsive genetic circuits for dynamic control of central metabolism

  • Xu, X
  • Li, X
  • Liu, Y
  • Zhu, Y
  • Li, J
  • Du, G
  • Chen, J
  • Ledesma-Amaro, R
  • Liu, L
Publication Date
Jul 30, 2020
UPCommons. Portal del coneixement obert de la UPC


Dynamic regulation is a promising strategy for fine-tuning metabolic fluxes in microbial cell factories. However, few of these synthetic regulatory systems have been developed for central carbon metabolites. Here we created a set of programmable and bifunctional pyruvate-responsive genetic circuits for dynamic dual control (activation and inhibition) of central metabolism in Bacillus subtilis. We used these genetic circuits to design a feedback loop control system that relies on the intracellular concentration of pyruvate to fine-tune the target metabolic modules, leading to the glucaric acid titer increasing from 207 to 527 mg l−1. The designed logic gate-based circuits were enabled by the characterization of a new antisense transcription mechanism in B. subtilis. In addition, a further increase to 802 mg l−1 was achieved by blocking the formation of by-products. Here, the constructed pyruvate-responsive genetic circuits are presented as effective tools for the dynamic control of central metabolism of microbial cell factories.

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