Leveraging biology to produce natural ingredients that power everyday life and replacing less effective ingredients with better, more economical alternatives promises to usher in the next generation of consumer products. But hurdles remain.
An often used phrase in biotech circles over the last ten years has been “industrializing biology”, which refers to automating lab processes to increase R&D throughput, increased modularity, and use of repeatable biological parts and pieces to make work more predictable and scalable. But another phrase has come up lately: “biologizing industry”. “Biologizing industry” means replacing myriad established chemical processes with biological ones. The same tools are deployed, but “biologizing industry” puts the accent in a new place — on discovery, novelty, and reinvention rather than optimization and efficiency at scale. Both are needed, but “biologizing industry” is a bolder vision.
For the past century, the chemical manufacturing ecosystem has been powered by synthetic chemistry. It’s an amazingly flexible tool for engineering basic ingredients used in both commodity and specialty markets, and its utility has been enabled by the availability of cheap feedstocks such as hydrocarbons and plant oils. But the recent development of new biological engineering tools allow us to survey the full diversity of nature, replicate desirable biochemical processes by way of microorganisms, and scale these molecules in manufacturing processes powered by industrial fermentation. This workflow can usher in the next generation of consumer products sourced and supplied from biology.
Equally important, “biologizing industry” implies the promise of moving us to a higher performance standard for the ingredients that make the products of everyday life. Rather than being limited to ingredients that are available via synthetic chemistry from cheap feedstocks and which perform well enough, we can locate more tailored and purpose-suited natural ingredients that are both cost competitive and better performing. Yet, removing the bottleneck of ingredient discovery is highlighting other pain points in the path to market. What will it take for this wave of new naturally sourced ingredients to live up to their potential in mass consumer markets?
Removing bottlenecks with biology
One oft cited example of tapping biological diversity for better performance is nootkatone. The standard manufacturing route used today relies on extracting the ingredient from citrus fruit byproducts, which is then used in specialty markets, such as in flavor and fragrance applications. Although nootkatone could be used more broadly, low yields from plant extraction produce the ingredient for more than $2,500 per kilogram. Thus, the ingredient is prohibitively expensive for use beyond its niche in the F&F market.
That could soon change. Industrial biotech companies such as Isobionics, Allylix, and Evolva are looking to produce nootkatone at substantially lower costs by utilizing engineered fermentations as the primary production route. Lower cost production could expand the market potential of nootkatone by tenfold, according to analysts at Edison.
Therein lies the promise of “biologizing industry”: leveraging biology as a manufacturing paradigm to position ingredients limited to niche markets today to compete head-to-head with chemically synthesized ingredients. Cultured ingredients (those produced from fermentation) can offer superior performance along with additional benefits including higher yields and purity, on demand production, and fewer process inputs. Moreover, industrial fermentation avoids agricultural challenges such as seasonality, crop blight, and citrus greening.
Substantiation is a challenge for novel ingredients
While the scaleable economics of fermentation will play a key role in expanding nootkatone’s potential, substantiating performance and delivering on consumer experience will be key to the ingredient finding real traction in new markets. Consider the market for insect repellents, which is currently dominated by the synthetically-derived ingredients DEET, permethrin, and picaridin. Each has the ability to repel disease-spreading insects for long durations at low concentrations and is relatively safe to humans. Their efficacy has established a high bar for challengers, but the opportunity to displace them seems ripe: synthetics like DEET have several factors detrimental to the consumer experience and, most importantly, the emergence of insects resistant to the ingredients has hastened the search for naturally derived alternatives that deliver “more and better”.
Some hope that cultured nootkatone, which has demonstrated the ability to serve as a potent insect repellent and insecticide, can become just such an ingredient. Although data are fairly limited and results have struggled with reproducibility, tests conducted to date by the Centers for Disease Control have provided enough encouraging data to warrant further investigation and investment.
- In laboratory testing, the CDC found that nootkatone had a mean RC50, or the concentration of a material that will repel half of a targeted population, of 0.0458% (wt/vol) compared to 0.0728% for DEET (lower is better). These numbers were not statistically significant, but suggest nootkatone could be an effective insect repellent.
- In laboratory testing, the CDC found that nootkatone had a mean LC50, or the lethal concentration of a material that will kill half of a targeted population, of 0.0029% to 0.0083% (wt/vol) for mosquitoes, ticks, and fleas — suggesting it may be one of the most effective insecticide compounds studied to date.
- In field tests, the CDC found that a 2% concentration of nootkatone could repel deer ticks in a wide area for 42 days with roughly 92% effectiveness.
Several entities are working to corroborate these results. Colorado State University is conducting field trials with funding from the National Institutes of Health, while Evolva is working toward regulatory registration of cultured nootkatone for use as a biopesticide and repellent.
In addition to efficacy, nootkatone could provide several benefits to the consumer experience of insect repellents. Take DEET as the standard. It has an unpleasant odor, is greasy, can persist in the environment, and can damage polyester fibers found in many consumer textiles. In comparison, nootkatone has a pleasant citrus scent, is non-oily, breaks down in the environment (it’s a terpenoid), and does not damage textile fabrics. If nootkatone can be shown to repel insects with the same efficiency and for the same long durations as DEET, then it may prove to be a superior product. For now, however, early optimism for the natural ingredient has yet to translate into demonstrated and reproducible results.
The next age of ingredient manufacturing
In addition to nootkatone, there are many other naturally occurring terpenoids and flavonoids with great antimicrobial and other useful properties, but that have their market potential limited by high production costs. The biotech revolution, enabled by the scalability and favorable economics of industrial fermentation, allows us to scan the wide array of biologically available materials for ones that suit an application or purpose with better functional activity and less waste compared to synthetically derived counterparts currently in use. That could enable these new candidates, the niche ingredients of today, to become the household names of tomorrow.
However, the most significant bottleneck for achieving “more and better” by using novel natural ingredients in mass market products is shifting from ingredient discovery to application testing and substantiation. For while the forest certainly does provide a virtually limitless set of molecules to assay, demonstrating their efficacy in a way that’s compelling enough to incite a shift from tried and true ingredients such as DEET is not trivial.