Harnessing Yeast for Health: The ABA Connection
Scientists explore yeast's role in producing Abscisic Acid for better health.
Femke Van Gaever, Paul Vandecruys, Yasmine Driege, Seo Woo Kim, Johan M. Thevelein, Rudi Beyaert, Jens Staal
― 6 min read
Table of Contents
- ABA and Animal Health
- Probiotics: The Friendly Microbes
- Yeast as a Probiotic
- Engineering a Yeast for Better Health
- Getting Results in the Lab
- Testing in Mice
- Understanding Why ABA is Low in Mice
- Temperature Trouble
- Tweaking the Yeast
- Enhancing Production
- The Collective Learning Experience
- More Attempts
- Future Directions
- The Delightful Takeaway
- Original Source
Abscisic Acid (ABA) is a plant hormone that plays a key role in helping plants deal with stress and grow properly. It helps plants cope with situations like drought or extreme temperatures. While scientists have studied its effects on plants extensively, only recently have they started to look at how it might work in animals, including humans.
ABA and Animal Health
Research suggests that ABA might also help animals with various health issues. For instance, it has shown promise in treating conditions like colitis, type 2 diabetes, atherosclerosis (which is related to heart health), and even depression. It's found in high amounts in fruits such as figs, bilberries, and apricots, making ABA an interesting candidate for a health-boosting food supplement.
However, ABA has some challenges that make it tough to use in supplements. For example, it doesn't last long in the body, can be costly to produce in large amounts, and can break down easily. This limits its usefulness as a direct supplement for people.
Probiotics: The Friendly Microbes
Probiotics are live microbes that can provide health benefits when consumed. They can help keep the gut healthy, and many people use them as dietary supplements. One type of probiotic that has been gaining attention is a YEAST called Saccharomyces boulardii. This yeast is generally recognized as safe and is often used to treat diarrhea and other gut-related issues.
In recent years, scientists have been getting creative with probiotics, using genetic engineering to enhance their abilities. For example, certain bacteria have been modified to fight infections or even provide treatments for diseases like cancer. But there's a downside: many probiotics can be affected by antibiotics, which means they might not work well if someone is taking medication.
Yeast as a Probiotic
While most studies on probiotics have focused on bacteria, researchers are now looking into yeast like S. boulardii. This yeast has shown great potential because it has unique properties that may help in producing beneficial substances like ABA.
Engineering a Yeast for Better Health
The quest began to create a special strain of S. boulardii that could produce ABA. To do this, researchers took specific genes from a mold called Botrytis cinerea, a natural source of ABA, and introduced them into the yeast. They aimed to create a yeast that could produce high levels of ABA while still being safe and effective.
Getting Results in the Lab
After modifying the yeast, scientists grew it in a lab to see how much ABA it could produce. They found that the engineered yeast produced about 8.5 to 8.6 mg of ABA per liter, which was quite good. However, the yeast didn’t grow quite as well as the unmodified strains, suggesting that there may be a trade-off between producing ABA and growing quickly.
Testing in Mice
To see how well their ABA-producing yeast worked in a living system, researchers decided to test it in mice. Rather than using the standard method of oral gavage (which sounds as unpleasant as it is), they cleverly created a special diet where the yeast was mixed into the food. This way, the mice could eat it more comfortably.
When the mice ate the yeast-supplemented diet, scientists detected high levels of the engineered yeast in their stool, indicating that the yeast was thriving in the gut. However, making sure that the yeast produced enough ABA in the body was the next challenge.
Understanding Why ABA is Low in Mice
Even though the yeast successfully colonized the gut, measuring ABA levels in the mice's serum showed surprisingly low results. This left many scratching their heads. Scientists discovered that the yeast likely produced much of the ABA before it was even eaten, meaning it could’ve been made while sitting in the feeding bowl. Not exactly what they hoped for!
Temperature Trouble
A significant issue was that the yeast's ability to produce ABA dropped sharply at the physiological temperature of the mice—37°C. While it worked well at 30°C, it struggled at higher temperatures. This highlighted a critical bottleneck: the yeast needed to get better at producing ABA at the body temperature of mammals.
Tweaking the Yeast
Researchers went back to the lab to improve the yeast's ability to produce ABA at higher temperatures. They focused on optimizing different parts of the production process to maximize ABA levels.
Enhancing Production
To boost ABA production further, they explored using additional genetic tweaks, such as integrating genes that help with the Metabolic Pathways involved in ABA synthesis. They added genes from other fungi that might help the yeast cope better at body temperature.
The Collective Learning Experience
Through numerous trials, the team found that by introducing various new genes, such as those that enhance certain metabolic pathways, they could improve ABA yield. They observed that while the yeast could survive, it wasn’t producing the desired ABA levels under the heat stress of 37°C.
More Attempts
In an effort to push the production even higher, scientists tried integrating genes that would allow the yeast to overcome these thermal limitations. They carefully selected genes known to help yeast withstand heat better and improve fermentation processes.
Future Directions
The research on ABA and its potential health benefits is still in its early stages. There’s much to explore about how this plant hormone can be effectively used as a nutraceutical. The hope is that further modifications will lead to a yeast strain that can produce substantial levels of ABA even at higher temperatures, allowing for its use in food supplements and possibly therapeutic applications.
The Delightful Takeaway
Even though the scientists faced many challenges in their journey to create a super probiotic yeast, the process was filled with surprising discoveries and learning moments. And who knows? Someday, this yeast might just help people feel better or even lead to new treatments. For now, this research lays the groundwork, and we can all be just a little more hopeful about the possibilities of nutrition and health coming from our tiny, little friends inside the yeast world.
So next time you enjoy your fruits, remember, it could be more than just a snack—it might hold the potential for future health benefits, thanks to some clever science!
Original Source
Title: Multi-Step Pathway Engineering in Probiotic Saccharomyces boulardii for Abscisic Acid Production in the Gut
Abstract: The plant hormone abscisic acid (ABA) has gained attention for its role in animals and humans, particularly due to its protective effects in various immune and inflammatory disorders. Given its high concentrations in fruits like figs, bilberries and apricots, ABA shows promise as a nutraceutical. However scalability, short half-life and cost limit the use of ABA-enriched fruit extracts and synthetic supplements. In this study, we propose an alternative ABA administration method to overcome these challenges. We genetically engineered a strain of the probiotic Saccharomyces boulardii to produce and deliver ABA directly to the gut of mice. Using the biosynthesis pathway from Botrytis cinerea, four genes (bcaba1-4) were integrated into S. boulardii, enabling ABA production at 30{degrees}C, as previously described in Saccharomyces cerevisiae. Introducing an additional cytochrome P450 reductase gene resulted in a 7-fold increase in ABA titers, surpassing previous ABA-producing S. cerevisiae strains. Supplementation of the ABA-producing S. boulardii in the diet of mice (at a concentration of 5 x 108 CFU/g) led to effective gut colonization but resulted in low serum ABA levels (approximately 1.8 ng/mL). The absence of detectable serum ABA after administration of the ABA-producing probiotic through oral gavage, prompted further investigation to determine the underlying cause. The physiological body temperature (37{degrees}C) was identified as a major bottleneck for ABA production. Modifications to enhance the mevalonate pathway flux improved ABA levels at 37{degrees}C. However, additional modifications are needed to optimize ABA production before testing this probiotic in disease contexts in mice.
Authors: Femke Van Gaever, Paul Vandecruys, Yasmine Driege, Seo Woo Kim, Johan M. Thevelein, Rudi Beyaert, Jens Staal
Last Update: 2024-12-23 00:00:00
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.12.22.629964
Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.22.629964.full.pdf
Licence: https://creativecommons.org/licenses/by/4.0/
Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.
Thank you to biorxiv for use of its open access interoperability.