Description
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Description

Our team has designed an effective biocontainment system utilizing cross-kingdom communication with bacteria via Acyl homoserine lactones (AHL).

As a first step of the project, we tested an inducible-irreversible genetic switch module and a cross-kingdom communication module for bacteria in Saccharomyces cerevisiae. Our biocontainment system utilizes both modules in combination with an effective toxin-antitoxin system.

  • Advantage of Modular Co-cultre Metabolic Engineering

    • Modular co-culture engineering optimizes biosynthesis by allowing metabolic pathway sharing among organisms, reducing individual metabolic stress, and increasing product yield[1].

  • Application & Prospects of Modular Co-culture Engineering in Pharmaceuticals

    • Traditionally, biological molecules like antibiotics are extracted from plants or fungi, which have slow growth and metabolic limitations. To overcome this, modular co-culture engineering is used by introducing natural product biosynthesis pathways into hosts, reducing metabolic stress. This approach has been applied to various phytochemicals [2, 3].

    Vitamin K2, considered for osteoporosis treatment, can be efficiently produced through modular co-culture engineering, boosting supply stability and affordability. Co-cultivation enhances production yield, reduces production time, and offers a cost-effective alternative [4].

    Noscapine, an anticancer drug, can be produced using engineered yeast, with higher efficiency expected through co-cultivation. It is considered for cancer treatment and can be produced more efficiently through co-culture [5].

    Challenges remain in chemical synthesis of plant-derived natural compounds, often necessitating extraction from plant biomass [5].

    However, recent research has shown that modular co-culture engineering has been applied to the production of artemisinic acid, a precursor to the antimalarial drug artemisinin [6]. This demonstrates the advancing technology that allows the production of plant-derived natural compounds using engineered yeast as a platform for co-cultivation.

    Moreover, modular co-culture engineering can reduce drug prices and offer societal benefits by resolving supply instability and fluctuations. For example, artemisinin production faced supply issues, and research led to more efficient biosynthesis [7].

  • [1] Chen, T., Zhou, Y., Lu, Y., & Zhang, H. (2019). Advances in heterologous biosynthesis of plant and fungal natural products by modular co-culture engineering. Biotechnology letters, 41, 27-34.
  • [2] Jones, J. A. et al. (2016). Experimental and computational optimization of an Escherichia coli co-culture for the efficient production of flavonoids. Metab. Eng. 35, 55–63.
  • [3] Jones, J. A. et al. (2017). Complete biosynthesis of anthocyanins Using E. coli polycultures. mBio 8, e00621–17.
  • [4] Yang, Q., Zheng, Z., Zhao, G., Wang, L., Wang, H., Ding, X., ... & Wang, P. (2022). Engineering microbial consortia of Elizabethkingia meningoseptica and Escherichia coli strains for the biosynthesis of vitamin K2. Microbial Cell Factories, 21(1), 1-16.
  • [5] Li, Y. & Smolke, C. D. (2016) Engineering biosynthesis of the anticancer alkaloid noscapine in yeast. Nat. Commun. 7, 12137.
  • [6] Ro, DK., Paradise, E., Ouellet, M. et al. Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440, 940–943 (2006). https://doi.org/10.1038/nature04640
  • [7] Paddon, C. J., Westfall, P. J., Pitera, D. J., Benjamin, K., Fisher, K., McPhee, D., ... & Newman, J. D. (2013). High-level semi-synthetic production of the potent antimalarial artemisinin. Nature, 496(7446), 528-532.