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Screening microbially produced Δ9-tetrahydrocannabinol using a yeast biosensor workflow

Author

Listed:
  • William M. Shaw

    (Boston University
    Boston University
    Imperial College London
    Imperial College London)

  • Yunfeng Zhang

    (Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences)

  • Xinyu Lu

    (Imperial College London
    Imperial College London)

  • Ahmad S. Khalil

    (Boston University
    Boston University
    Harvard University)

  • Graham Ladds

    (University of Cambridge)

  • Xiaozhou Luo

    (Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences)

  • Tom Ellis

    (Imperial College London
    Imperial College London)

Abstract

Microbial production of cannabinoids promises to provide a consistent, cheaper, and more sustainable supply of these important therapeutic molecules. However, scaling production to compete with traditional plant-based sources is challenging. Our ability to make strain variants greatly exceeds our capacity to screen and identify high producers, creating a bottleneck in metabolic engineering efforts. Here, we present a yeast-based biosensor for detecting microbially produced Δ9-tetrahydrocannabinol (THC) to increase throughput and lower the cost of screening. We port five human cannabinoid G protein-coupled receptors (GPCRs) into yeast, showing the cannabinoid type 2 receptor, CB2R, can couple to the yeast pheromone response pathway and report on the concentration of a variety of cannabinoids over a wide dynamic and operational range. We demonstrate that our cannabinoid biosensor can detect THC from microbial cell culture and use this as a tool for measuring relative production yields from a library of Δ9-tetrahydrocannabinol acid synthase (THCAS) mutants.

Suggested Citation

  • William M. Shaw & Yunfeng Zhang & Xinyu Lu & Ahmad S. Khalil & Graham Ladds & Xiaozhou Luo & Tom Ellis, 2022. "Screening microbially produced Δ9-tetrahydrocannabinol using a yeast biosensor workflow," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33207-x
    DOI: 10.1038/s41467-022-33207-x
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    References listed on IDEAS

    as
    1. Brian Owens, 2019. "The professionalization of cannabis growing," Nature, Nature, vol. 572(7771), pages 10-11, August.
    2. Elie Dolgin, 2019. "The bioengineering of cannabis," Nature, Nature, vol. 572(7771), pages 5-7, August.
    3. Liam Drew, 2019. "Cannabis research round-up," Nature, Nature, vol. 572(7771), pages 20-21, August.
    4. Xiaozhou Luo & Michael A. Reiter & Leo d’Espaux & Jeff Wong & Charles M. Denby & Anna Lechner & Yunfeng Zhang & Adrian T. Grzybowski & Simon Harth & Weiyin Lin & Hyunsu Lee & Changhua Yu & John Shin &, 2019. "Complete biosynthesis of cannabinoids and their unnatural analogues in yeast," Nature, Nature, vol. 567(7746), pages 123-126, March.
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    1. Charlotte Cautereels & Jolien Smets & Peter Bircham & Dries De Ruysscher & Anna Zimmermann & Peter De Rijk & Jan Steensels & Anton Gorkovskiy & Joleen Masschelein & Kevin J. Verstrepen, 2024. "Combinatorial optimization of gene expression through recombinase-mediated promoter and terminator shuffling in yeast," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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