Polyamines with known functionalities can treat age-related disorders

According to a new scientific study, recently published in the Nature Catalysis journal, baker's yeast can be engineered and improved to create polyamines and polyamine analogs to address major problems in both the health and agriculture sectors.

Polyamines with known functionalities can treat age-related disorders
Image Credit: Technical University of Denmark

The Earth's population is expanding, and individuals are projected to live longer lives in the days to come. Hence, improved and more dependable treatments for human disorders, like cardiovascular and Alzheimer’s diseases, are very critical.

To address the problem of ensuring healthy aging, a team of international researchers explored the possibility of biosynthesizing various polyamines and polyamine analogs with already familiar functions for treating and preventing age-related disorders.

Spermidine is one of the most intriguing compounds to investigate in this context. It is a natural product that already exists in people’s blood and induces autophagy—a crucial cellular process for removing damaged proteins—such as misfolded proteins in brain cells that is responsible for causing Alzheimer’s disease.

As people age, the level of spermidine in their blood reduces, and dietary supplements or specific food products are required to maintain a constant and high level of spermidine in the blood.

But due to their structural complexity, such products are difficult to manufacture using traditional chemistry, and extraction of natural resources is neither sustainable nor financially viable. Hence, the researchers chose to use their biochemical toolbox and employ conventional metabolic engineering techniques to design the yeast metabolism to create polyamines and polyamine analogs.

This group of molecules has huge potential in addressing important societal challenges and it seemed logical to try and produce them with the help of biology."

Jiufu Qin, Senior Researcher, The Novo Nordisk Foundation Center for Biosustainability

Solid vantage point

The researchers investigated seven biosynthetic pathways that produce spermidine from ornithine or arginine, and by using flux balance analysis, the team can predict the highest theoretical yield of each route.

After identifying the most effective spermidine route and methodically manipulating the yeast’s cellular metabolism, the researchers were able to produce spermidine at titers of 2.3 g per liter on a laboratory scale.

A preliminary result confirmed the viability of harnessing nature’s vast and diverse reservoir of biochemical tools to advance products that can address the issue of aging population and the shortage of adequate food supply.

We expect that our studies lay the groundwork for fermentation-based manufacture of diverse polyamines and polyamine analogues to further unlock this field’s potential for pharmacological and agricultural applications."

Jens Nielsen, Professor, Chalmers University of Technology and CEO, BioInnovation Institute

However, all that glitters is not gold, and an impediment, like a low-enzyme activity that causes feedback regulation and thus affect the product yield, still needs to be resolved.

Hit the nail on the head

Although the strain may need to be enhanced further, upgrades to commercial production are already underway because the present-day titers are considered to be adequate for starting the production.

Based on this scientific study, the firm Chrysea Labs was established with the goal of making healthy lifespan nutritional interventions by improving the autophagy—the naturally occurring anti-aging mechanism—that recycles the cellular process. This process is critical for maintaining the health, survival, and renewal of cells.

Since the industry is projected to increase in the future and just a few rivals are now working in the sector, Chrysea Labs may have a window of opportunity to be a pioneer in ensuring healthy aging.

Source:
Journal reference:

Qin, J., et al. (2021) Engineering yeast metabolism for the discovery and production of polyamines and polyamine analogues. Nature Catalysis. doi.org/10.1038/s41929-021-00631-z.

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