The Reinvention of the Chemical Industry

With help from Enginzyme

Globally, the production of chemicals accounts for 7% of all industrial greenhouse gas emissions. Before 2050, the industry needs to cut its own emissions by half, while at the same time quadrupling production to meet growing demand.

When I first learned of this, I thought “Hmm. Guess those science experiments are using quite a few chemicals, huh?” But as it turns out, the chemical industry affects many more aspects of our lives than just our high school lab experience.

In other words, the industry affects everything from our water supply, food, shelter, clothing, healthcare, technology, and even the way we get around — aka, basically everything.

What’s fortunate is that, in recent years, advances in the game-changing field of synthetic biology have started a transformation in the chemical industry and beyond.

While there is no fixed definition of synthetic biology my friend Sofi Sanchez mentions in her article:

There is no fixed definition of synthetic biology. But (in her words),
synbio = the expansion of biotechnology as a multidisciplinary field that seeks to create new biological parts, devices, and systems, or redesign already existing ones, so that they produce a substance, or gain a new ability by combining engineering principles with biology.

So how exactly does synthetic biology tie in with the chemical industry?

One word: biomanufacturing (and industrial biotechnology).

Biomanufacturing is a type of production that uses biological systems to construct commercially-relevant biomaterials to add to diverse fields like the production of chemicals.

Tying to this, industrial biotechnology is simply exploitation of enzymes, microorganisms, and plants to produce energy, industrial chemicals and consumer goods using biomanufacturing techniques.

Interestingly, this technology is not new — Industrial biotechnology has been around since at least 6000 B.C., when Neolithic cultures fermented grapes to make wine and Babylonians brewed beer with microbial yeasts.

Over the years, our understanding fermentation has allowed us to take this further and create everyday foods like cheese, yoghurt, vinegar, and other products.

Fast forward a little later to the 1940s, and large-scale fermentation processes were developed in order to produce industrial amounts of penicillin, which Sir Alexander Fleming isolated from mould in 1928.

So what is fermentation? How does it work?

In biology, fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes.

In biotechnology, fermentation is the intentional use of fermentation by microorganisms like bacteria, fungi, or eukaryotic cells to make products useful to humans.

Today, fermentation is an important part of the production process for key compounds like ethanol, organic acids, butanol, amino acids, surfactants, biodegradable polymers, antibiotics, vitamins, industrial enzymes, biopesticides, biopharmaceuticals and more.

Here’s a rundown of how fermentation works:

  1. A cell is selected based on its ability to produce the desired product
  2. A seed stock of cells is put into a small amount of media, which provides the nutritional products the cell needs to grow
  3. When the population of cells has grown and consumed most of the nutrients, it’s moved into a larger vessel with more growth media and the process repeats
  4. When the quantity of cells is large and healthy enough, the cells are transferred into a production vessel often referred to as a bioreactor or fermenter. With plenty of fresh media now available under tightly controlled conditions, the cells grow and manufacture product
  5. After the fermentation is complete, the product is harvested

When tied to synthetic biology, fermentation is often combined with gene editing, making a typical synbio production process look like this (example given relates to food production):

  • Synthetic biologists identify the gene sequences that give food or fiber certain qualities
  • The gene sequence for that protein is created chemically in a lab and inserted into yeast or bacteria cells
  • A fermentation process turns the microbes into tiny factories that mass produce the desired protein — which is then used as a food ingredient, as example

Although this idea sounds miraculous conceptually, the problem is that the complexity and cost of processes like these are limiting the potential of impact made by synthetic biology in the chemical realm.

On one hand, reprogramming a cell to do something it wasn’t supposed to do frequently necessitates significant investments in robotics and DNA synthesis.

Another drawback is that in order for cells to stay alive, energy is diverted to simply allow the cells to sustain, which adds nothing to the desired result but does up the $$. These two factors raise the cost of fermentation and stymie the development of biological manufacturing, which is really cost-competitive with existing chemical manufacturing techniques.

In Comes EnginZyme

To address these same issues, Karim Cassimjee took his vision to make the chemical industry green using enzymes and started EnginZyme in 2014.

Enginzyme on their way to relieve key bottlenecks in industrial biotech 🧪

The company’s approach relates to conventional fermentation, but with a twist. While current fermentation tech takes advantage of bacteria to be the producers and mixers of the useful enzymes that produce chemicals, EnginZyme’s approach is to attach solid particles to the enzymes, and put them in a compact vessel which acts like a factors.

Ingredients flow in, getting to the fixed enzymes, and the resulting output, which is the final product, flows out the other end — essentially mimicking a metabolic pathways, except with immobilized enzymes acting as the catalyst.

The benefits

By removing the enzymes from the cell rather than modifying the whole organism (and using biocatalysts rather than metal), they’re able to unlock the door to smaller-scale, on-demand manufacturing, marrying biology with industrial chemical process technology.

One example of this is that, once the cell is engineered to be stable for an extended period of time — a necessary precursor to the immobilization process— the enzymes are put onto a solid material, as mentioned earlier, and then used in a packed bed reactor.

Source

A packed bed reactor is one that is frequently used in the chemical industry. They’re very versatile and are used in chemical processing applications such as absorption, distillation, stripping, separation processes, and catalytic reactions, demonstrating how EnginZyme is pioneering a merge with conventional chemical industry and synbio.

Ultimately, the result substantially reductions in the environmental impact of chemical processes while simultaneously greatly improving their economics.

Current Status

In late April of 2020, EnginZyme announced that they raised €6.4 million in a Series A — and since then, they’ve come a long way. Just last week, EnginZyme announced that they’d reached a significant milestone in their experiments,

As reported by WagmTV:

From April to August 2021, a pilot was designed to prove the feasibility of manufacturing at a commercial scale. It involved using EnginZyme’s technology platform along with enzymes provided by Ghent University to produce a low-calorie rare sugar, called kojibiose, which is naturally present in honey.

The result showed that compared to fermentation processes, the space-time yields and product titers are significantly higher, thereby successfully demonstrating the potential for a highly cost-efficient process. This strengthens the promise of sustainable biomanufacturing of a multitude of products.

“We have reached an important breakthrough as we now can demonstrate our ability to design, create and validate a commercial process at a large scale” said CEO and co-founder Karim Engelmark Cassimjee. “Delivering these significant product volumes, already at our early stage of development, further strengthens our leadership position in the cell-free biomanufacturing field and is a major step towards using our technology broadly.”

“The EnginZyme cell-free biomanufacturing technology is impressive, and we were extremely satisfied with the smooth scale-up and robust performance of the technology,” said Muriel Dewilde of Bio Base Europe Pilot Plant.

Future Hopes

As per an interview with Forbes, Cassimjee wants to transform the entire chemical industry, from plastics to bulk chemicals.

However, it won’t exactly be a piece of cake. “For each application, we have to produce a chemical process and production plant,” he says.

At the end, the “holy grail” will be coming up with a proven, large-scale production strategy for making whatever it is the world needs from chemistry — but however challenging, with the recent advancements, I wouldn’t doubt them.

Interested in innovation and always ready to learn more!