From Forest Fungi to Pharmaceutical Breakthrough
The design of everyday shipping pillows served as the low-cost, sterile bioreactors for producing life-saving pharmaceutical ingredients. Since the interior of these air pouches is sterile, it acts as a perfect environment for wood-derived glucose to undergo the chemical process needed to result in fungi-derived enzymes. Researchers simply inject the reaction mixture into the pouches and rock back and forth, which provides high-oxygen aeration while bypassing the need for expensive laboratory equipment. This creative use of common materials helps reduce production costs by more than 60%.
Over two decades ago, researchers at the USDA Forest Service Forest Products Laboratory were studying a seemingly mundane topic: how wood rots. Specifically, they were trying to better understand the enzymes that white rot fungi use to break down trees, in hopes that a cleaner method for producing paper could be found. Fast forward to today, and that basic research has led to an unexpected new cost-effective approach to producing a key ingredient in life-saving medications.
The centerpiece of this new discovery is a molecule named (S)-3-hydroxy-γ-butyrolactone, mercifully shortened by scientists to HBL. While the name might not ring a bell, this molecule is vital to the manufacturing of some critical pharmaceutical drugs, such as cholesterol-lowering statins, HIV inhibitors, and a range of antibiotics. Currently, HBL costs a staggering $450 per kilogram, and relies on petroleum-based and energy-intensive production procedures.
“Our new method for producing HBL combines biological and chemical steps,” explains Nathaniel Kuch, a chemist with the Forest Products Laboratory. “The biological portion uses two enzymes from white rot fungi to convert glucose sugar into a highly reactive molecule.”
This biological conversion utilizes what might be the most unconventional bioreactor ever—inflatable shipping pillows—the type of material you might find in an everyday Amazon package. This ingenious low-cost idea was developed by Forest Products Laboratory research microbiologist Phil Kersten, a lead inventor of this process, and allows researchers to fill the pillows with the high levels of oxygen required for high reaction efficiency.
“We just add the glucose and bacteria containing the enzyme that do the first reaction, then do the second reaction very similarly with bacteria containing a second enzyme” says Casey Crooks, a research microbiologist with the Forest Products Laboratory. “After these biological reactions take place, we are left with a ‘trione’ – a highly reactive intermediate substance.”
The next stage employs a chemical reaction, where the trione is passed over a catalyst at room temperature, which produces the sought-after HBL. This process is far simpler than the high-energy, expensive methods currently in use.
When researchers modeled this new workflow at the industrial scale, the results surprised even them.
“This new technique for HBL production results in an estimated cost of $162 per kilogram—a far cry from the estimated current $450 per kilogram price tag,” says Kuch. “This is a 64% improvement and doesn’t even include steps we could take to further optimize the system.”
The cost savings could have ripple effects far beyond the pharmaceutical industry. Currently, HBL’s high cost severely restricts its use; however, a more affordable supply could unlock new markets. The Department of Energy has identified HBL as a valuable precursor not just for drugs but potentially for other useful applications, such as biodegradable plastics.
This new process of obtaining HBL fits naturally into the forest products industry. As production of high-value nanocellulose from trees gains traction, an inevitable byproduct is glucose. Rather than discarding this glucose as a waste product, it could be used in HBL production, potentially strengthening rural economies by introducing a new valuable product for forest products mills and the communities that depend upon them by turning what was a byproduct of forest management into a pharmaceutical-grade product.
“The path from discovery to publication of this method was a long one,” reflects Crooks. The research began as a joint venture agreement in 2018 with the USDA Forest Service, University of Wisconsin-Madison, and the University of Maine. This type of cross-institutional collaboration is central to the way in which the Forest Service produces impactful results that are larger in scope than what any single institution could deliver on its own. Through this partnership, researchers filed two new patents—one being for the ingenious use of shipping pillows as bioreactors.
This pioneering work represents more than simply face value cost savings; it offers a glimpse at a future where forest products and present-day forest waste can be converted into highly sought-after commodities and where basic scientific curiosity—in this case originally about white rot fungi—can lead to breakthrough scientific discoveries.