4.7 Article

A p-Coumaroyl-CoA Biosensor for Dynamic Regulation of Naringenin Biosynthesis in Saccharomyces cerevisiae

Journal

ACS SYNTHETIC BIOLOGY
Volume 11, Issue 10, Pages 3228-3238

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.2c00111

Keywords

yeast; flavonoids; transcriptional regulation; transcription repressor; dynamic pathway control

Funding

  1. European Union's Horizon 2020 research and innovation programme [814650]

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This study presents a novel biosensor that can respond to the central precursor p-coumaroyl-CoA and combined with a previous biosensor to regulate naringenin production. The results showed a significant increase in naringenin titer using this dual regulation approach.
In vivo biosensors that can convert metabolite concentrations into measurable output signals are valuable tools for high-throughput screening and dynamic pathway control in the field of metabolic engineering. Here, we present a novel biosensor in Saccharomyces cerevisiae that is responsive to p-coumaroyl-CoA, a central precursor of many flavonoids. The sensor is based on the transcriptional repressor CouR from Rhodopseudomonas palustris and was applied in combination with a previously developed malonyl-CoA biosensor for dual regulation of p- coumaroyl-CoA synthesis within the naringenin production pathway. Using this approach, we obtained a naringenin titer of 47.3 mg/L upon external precursor feeding, representing a 15-fold increase over the nonregulated system.

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