Part:BBa_K3419001

Tricosanthin

Usage and Biology

Note: All work on this basic part was done virtually through literature research due to COVID-19 restrictions.

Trichosanthin is a protein derived from Trichosanthes kirilowii, also known as the Chinese cucumber. It has been used in Eastern traditional medicine as an abortifacient and also functions as an antitumor agent due to its inactivation effect on eukaryotic ribosomes [1]. Trichosanthin is used in our project as an anti-cancer therapeutic protein that selectively kills tumor cells while leaving our engineered prokaryotic E. coli unaffected. We were able to confirm that E. coli would be able to produce this therapeutic based on a literature search (SOURCE #: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1399-3011.1992.tb01558.x). Thus, our bacteria would perform their intended function in our genetic circuit

Mechanism

Upon release into the cell, trichosanthin exhibits RNA N-glycosidase activity and depurinates the 28S rRNA of the 60S eukaryotic ribosomal subunit. This will achieve irreversible inactivation of eukaryotic ribosome activity and inhibit tumor cell function.

Figure 1. Trichosanthin is an inhibitor of protein synthesis that acts on mammalian ribosomes. Upon release into the cell, it exhibits RNA N-glycosidase activity and depurinates the 28S rRNA of the 60S eukaryotic ribosomal subunit. This will achieve irreversible inactivation of ribosome activity and inhibit tumor cell function.

References:

[1] Li, M. X., Yeung, H. W., Pan, L. P., & Chan, S. I. (1991). Trichosanthin, a potent HIV-1 inhibitor, can cleave supercoiled DNA in vitro. Nucleic acids research, 19(22), 6309–6312. https://doi.org/10.1093/nar/19.22.6309