Scientists have designed yeast to transform one of human’s most abundant waste into high-value biomaterials worth more than $80 per kilogram.
The new “bone protein” platform converts human urine into hydroxyapatite, the calcium phosphate mineral that forms bones and teeth, providing environmental and economic benefits to global waste management systems.
Researchers at Lawrence Berkeley National Laboratory, University of California, Irving and the University of Illinois have developed synthetic biology methods by modifying the candy therapy Boulardii, a cold-resistant yeast that naturally stores minerals in a dedicated honeycomb chamber called vacuoles.
Skeleton builders who imitate nature
Breakthroughs come from observing how osteoblasts (cells responsible for animal bone formation) create hydroxyapatite through complex multi-steps. These specialized cells accumulate calcium and phosphate in the acidic compartment, and then package the material into vesicles that crystallize bone minerals.
“The accidental part is that the yeast already has a similar molecular mechanism,” said Yasuo Yoshikuni, head of the DNA synthesis science program at the Joint Genome Institute. “Just a mild adjustment is enough to convert the yeast into a cell factory of hydroxyapatite.”
The engineering only requires the addition of two genes: one for urea dezyglass and the other for urea transporter. When the yeast breaks down urea from the urine, it raises the pH inside the cells, triggering a calcium pump that floods the vacuole with mineral components.
Cell assembly line
The team used advanced microscopy technology to accurately track how bone leaves were produced. This process begins when calcium and phosphate accumulate in the acidic vacuole as amorphous particles, which is stabilized by naturally occurring polyphosphate molecules.
Next, these loaded mineral vacuoles are converted into extracellular vesicles, which are secreted from the cells. Once outside, vesicles can merge together, while the enzyme breaks down the stable polyphosphate. This triggers the crystallization of the amorphous substance into platelet hydroxyapatite crystals.
It is worth noting that this crystallization occurs at a relatively low pH level of about 5.2, which is lower than the highly alkaline conditions usually required for the production of synthetic hydroxyapatite. The researchers suspect that the protein secreted with mineral vesicles is a template, similar to collagen guiding bone formation in vertebrates.
Turn waste into wealth
This technology addresses pressing challenges in wastewater management. Although urine accounts for only 1% of the total wastewater volume, it contains 70-90% nitrogen and 50-65% phosphorus in the waste stream – nutrients that can cause environmental problems when released to the waterway.
Current urine recycling efforts focus on the production of low-value fertilizers worth $300-400. However, due to the use of hydroxyapatite in orthopedic surgery, dental applications and water purification systems, premium prices are over $80 per kilogram.
The productivity of the bone platform exceeds 1 gram of hydroxyapatite per liter of urine. Economic modeling of cities large and small in San Francisco shows that the process could generate about $1.4 million in annual profits while significantly reducing wastewater treatment costs.
Key Production Advantages
This biological method has several advantages over conventional hydroxyapatite manufacturing:
- Use existing phosphorus and urea in fresh urine instead of requiring chemical input
- Operate under mild reaction conditions suitable for distributed applications
- Produce highly selective hydroxyapatite that is relatively insensitive to reaction changes
- Generate aggregates and nitrogen-rich fertilizers from the same raw materials
Beyond the bones
The research team envisions extending the application beyond hydroxyapatite production. The same engineering principles can enable yeast to produce other biominerals, or selectively extract valuable elements from the waste stream for environmentally friendly biologic operations.
“Today, we use about 1% of the world’s energy to make fertilizers from nitrogen,” Yoshikuni explained. “If we can produce hydroxyapatite at the same time and produce nitrogen fertilizer from ammonia, we can potentially replace a large portion of the total nitrogen demand; conserve energy, while also greatly reducing the cost of wastewater facilities.”
The patented ossification technology is now available for license and has the potential to provide new avenues for sustainable biomaterial production for human waste streams.
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