Wednesday 19 May 2021

Redesign of Terpenoid Biosynthetic Pathway in Plant by Genome Editing toward Human Health

I would like to share with all of you my experience when I joined a student exchange program at Bioengineering, Osaka University, Japan. I was there for a month and attended some lectures which were very exciting to share with all of you.

The first topic was presented by Prof. Dr. Toshiya Muranaka

Topic 1: Redesign of Terpenoid Biosynthetic Pathway in Plant by Genome Editing toward Human Health

Figure source: National Human Genome Research Institute (NIH), December 08, 2015

 

Plants are well documented as a great source of bioactive compounds used in many industrial productions. Among them, terpenoids, derived from terpenes, are specialized plant metabolites that have important functions in plant defense against biotic and abiotic stresses, and acting as signaling molecules. These metabolites have been importantly used for pharmaceutical industries. 

Fig. Structures of various terpenes

Terpenes with anti-inflammatory function. Numerous studies in recent decades have demonstrated that terpenes exert anti-inflammatory effects by inhibiting various proinflammatory pathways in ear edema, bronchitis, chronic obstructive pulmonary disease, skin inflammation, and osteoarthritis.

Terpenes and tumor. Terpenes have been exhibited to exert anti-tumorigenic effects against such processes in a number of in vivo and in vitro systems, thus indicating their potential uses as chemotherapeutic agents for treating tumors.

Terpenes and neuronal health. Numerous researches have demonstrated that essential oils derived from various plants have neuroprotective effects against neurodegenerative conditions in vivo and in vitro. Thus, as a main component of plant essential oils, terpenes may be beneficial to human neuronal health. However, only few studies have focused on the beneficial effects of terpene components of plant essential oils on neuronal health.

 Genome Editing in Potatoes

Through powerful genome-editing technologies, i.e., Zinc-Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs) and Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR/Cas), the increase and/or decrease of diverse metabolites productions can be realized. 

For instance, using genome-editing technologies to target POTATO CLYCOALKALOID BIOSYNTHESIS1 (PGA1) and PGA2 genes which encode cytochromes P450s (CYPs) for reducing steroidal glycoalkaloid (SGA) compounds in potato has been successfully applied. SGAs are abundant poisons in tuber sprouts and green tubers and are described as bitter tasting, burning, scratchy, or acrid. Producers and consumers have called for the removal of SGAs from potatoes. Only potato with SGAs of major food crops has such broad industry consensus on the need to solve this important worldwide problem. Controlling the SGA content is also important for potato breeding. Finally, the knockdown plants produced very little these kinds of poisonous compounds and changed their phenotypic characteristics. 

 

Read also: CRISPR/Cas Systems and Their Application for Genome Editing

 

OPINION AND COMMENT

In my opinion, these kinds of genome-editing technologies are really promising and useful for the future of human beings. With regard to bioethics, the utilization of these techniques for the right purposes will open a new window to solve global problems, such as environmental damages, human diseases, and even social economies. However, it is also possible to get an ‘off-target mutation effect’ during the editing process, generating some risks associated with downstream attributes. In particular, this incident can cause unwanted mutations that possibly undetected by the current technologies. Thus, if these unintended genetic modifications are incorporated into the genome, potentially those genes can be transferred onto other organisms. Once they become part of the cycle, those genes are then in the environment, leading to ‘genetic drive’ phenomena.

References

Cho, K. S., Lim, Y. R., Lee, K., Lee, J., Lee, J. H., & Lee, I. S. (2017). Terpenes from Forests and Human Health. Toxicological research, 33(2), 97–106. 

Umemoto, N., Nakayasu, M., Ohyama, K., Yotsu-Yamashita, M., Mizutani, M., Seki, H., ... & Muranaka, T. (2016). Two cytochrome P450 monooxygenases catalyze early hydroxylation steps in the potato steroid glycoalkaloid biosynthetic pathway. Plant physiology, 171(4), 2458-2467.

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