It seems as though every week a new piece of devastating news emerges to remind us of the ways our actions are damaging our planet. Advances in technology, chemical processes, farming, and healthcare have led to life-changing capabilities — but they haven’t come without serious side effects. From the bushfires in Australia to contaminated drinking water devastating entire communities, we find ourselves simultaneously in one of the greatest and most concerning time periods of Earth’s history. But there is hope. We can make industrial processes greener, figure out how to feed the planet, and sustainably eliminate waste — all by turning to biology, and by designing it to be even better.
Enzymes are the proteins behind life. They make reactions happen. Civilizations have been using enzymes for thousands of years; the most familiar examples being cheese, wine, and other fermented foods produced through microbial fermentation of sugars into alcohol. But enzymes aren’t just for producing delicious foods and beverages, and with the passing of time and development of tools and technology, we’ve learned how to leverage and even design microorganisms to make a veritable cacophony of different enzymes for different applications.
Industrial enzymes — enzymes produced for commercial use across a variety of industries — have already made certain everyday activities friendlier to the environment. Your clothes get just as clean from an energy conserving cold-water cycle as they do from a hot-water one, for example, thanks to industrial enzymes. Alternative fuels such as ethanol are also available to the world thanks to industrial enzymes. And harsh processes for producing our favorite clothes, such as jeans, are being made less so through the use of enzymes.
Industrial enzymes are the poster child for engineering a better future: they reduce water use, slash emissions, and minimize toxic byproducts often associated with chemical production. It may seem as though the world at large has only recently begun paying attention to and trying to do something about the issue of climate change, but some organizations were trying to head off this problem decades ago. And they were doing it with enzymes.
The birth of an industry
While we’ve been leveraging enzymes for thousands of years, it was only in the past 50 that industrial enzyme production became feasible on a large scale. It wasn’t until the 1980s when a perfect storm of recombinant DNA technologies (first used for biopharmaceutical applications), protein engineering capabilities that expanded the range in which enzymes could operate, and advances in microbial expression systems enabled the birth of an industry that has impacted everything from health care to biofuels to agriculture.
Indeed, once rDNA technologies expanded from biopharma to non-medical applications such as food, agriculture, and consumer products, it didn’t take long for the first engineered enzyme produced on the ton scale through microbial fermentation to make it to consumers. The company to produce the enzyme? Genencor. The product into which the company got their enzyme? None other than Procter and Gamble’s Tide laundry detergent. The story of how protein engineering was applied to enzyme production and brought to scale is one of the true success stories of modern biotechnology, says Joseph McAuliffe, who joined Genencor in 2000 as a scientist with a background in carbohydrate chemistry.
Greening up with biology
In the early 80s, Genentech created an offshoot company called Genencor. Genentech — then as now — was focused on biopharma, but the industry giant also recognized the wider relevance of industrial biotechnology. So, they partnered with Corning to create a spin-off company dedicated to industrial biochemical and enzyme production. It was a move that paid off.
The Genencor team leveraged rapidly improving protein engineering technology while also doing a significant amount of work to optimize the bacterial and fungal strains they used to produce their enzymes. These efforts not only got their enzyme, a protease, into Tide, but solidified Genencor as a pioneering organization in the field of industrial enzymes.
The company structure has changed quite a bit from those early days. Due to a series of acquisitions and mergers, McAuliffe is now a Senior Principal Scientist at an organization called DuPont Nutrition and Biosciences, which plans to spin off from DuPont and merge with the American Corporation International Flavors and Fragrances (IFF). But mergers and acquisitions aside, McAuliffe says the overarching goal of the company is still the same as it was over 30 years ago: to use biology to put the chemical and consumer products industries on a greener footing.
Significant strides have been made toward that end by DuPont and others — the spectacular success of enzymes is a case in point. But, McAuliffe says, the industry has struggled to meet that goal in other ways.
“The grand vision of industrial biotechnology [was always] getting rid of nasty old polluting chemical-based processes for making things, and doing it with biology — whether that’s monomers for plastics, vitamins, or biofuels,” says McAuliffe. “[But] that’s been a lot harder to do in reality, mostly due to commodity chemical economics rather than technical obstacles. When you look at the number of large scale biological processes for making chemicals, there haven’t been too many new processes brought to the world, with some notable exceptions, and so further penetration into the chemical production industry using enzymes and whole cell biocatalysts is needed in order to meet this original goal.”
The challenge is multi-faceted. Biology is certainly part of it, as it is with any life-sciences based endeavor. Echoing the sentiments of synthetic biologists the world over, McAuliffe says that what the industrial biotechnology industry needs is “better tools for high throughput screening and automated strain construction, like what Inscripta is doing, and better ways of designing proteins from scratch, like what Arzeda is trying to do. We are good at protein engineering but we can be better,” he continues, adding that “we [the industry] clearly recognize the need for improved tools and methods to more rapidly design function from first principles.”
Nevertheless, the engineering challenge to actually apply and scale improved technologies shouldn’t be ignored either, stresses McAuliffe, pointing to the example of cellulosic ethanol. Companies have been trying for years, and the government has injected significant funds, but still no one has figured out a cost-effective way to make ethanol from non-starchy parts of the plant. In this case a significant problem relates to the handling of tons of plant solids laced with soil, string, and other stuff to get something clean enough for enzymes to chew on.
So for now, the alternative fuels market isn’t yet growing at a substantial rate – and the existing incentives need to increase further to encourage the industry to pursue this technically challenging application. Given that, companies in the industrial enzymes space need to find new large-scale applications, and, says McAuliffe, the new opportunity has to be big for it to be interesting enough to follow up on. For Nutrition and Biosciences, interesting, big opportunities come from “expanding the box.”
Expanding the box
Enzymes are just proteins — the industrial fermentation methods for making them can be used to make any protein, enzyme or not. And when it comes to producing proteins on an industrial scale, opportunity spaces can be identified by exploring novel opportunities beyond just industrial enzymes. One of the biggest beyond-the-box opportunities today is the alternative meat space — and Nutrition and Biosciences is already in on it, supplying soy protein to this rapidly growing industry. The organization is also actively exploring opportunities in the commodity proteins and higher value proteins spaces, looking at proteins with novel physical properties to perform tasks such as emulsification, but that aren’t necessarily enzymes.
Regardless of the opportunity space, the driving motivation is to use biology to do things more efficiently and sustainably. This vision is one that the industry as a whole hasn’t done a great job of putting forth, despite the fact that it has been the driving factor behind new innovation in the space since the beginning. Really, says McAuliffe, “that’s what motivates us [the industry]. We’re not working in a field where we can point to the individual people we’ve saved because of some new drug, but we do believe collectively that biotechnology is essential for the world’s benefit in the 21st Century.”
And the benefits aren’t just the obvious. Aside from reducing raw material, energy and water consumption, and harmful carbon emissions, new and sustainable production processes can inject lifeblood into struggling rural economies, says McAuliffe. Take impoverished parts of the Midwest, he says, where the only real economic opportunity is agriculture. “One of the big mega trends is rural regions suffering from brain drain,” he says. “Our industry has the opportunity to enable regional economies and enable regional economic growth by creating jobs and opportunities.”
I’ve often heard it said that the solution to some of our biggest problems has been right in front of us all along, right there in nature. Biology is the most elegant, complex toolbox available to humanity, and enzymes are some of the most powerful tools in that box. By combining the best technological advances with the best of biology, we really can ensure a cleaner, more sustainable future, a future where ravaging bush fires and deaths from contaminated water and air are nothing more than a scary part of ancient history.8