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Sustainable and economic biocatalysis using Rotating Bed Reactors

Biocatalysis is the use of enzymes for making chemical transformations more efficient. Offering a number of benefits, it is becoming increasingly attractive to manufacturers of pharmaceutical ingredients and other products.

The attention paid by industry to the tremendous benefits of biocatalysts becomes apparent when reading the numbers. The market is estimated to grow at 6.4% per year reaching more than 240,000,000 kg of biocatalyst sold in 2032. Pharmaceutical companies, food & beverage producers and chemical manufacturers share many common ambitions:

  • Limit their environmental impact
  • Decrease their use of hazardous solvents and substances
  • Innovate processes compliant with the principles of green chemistry
  • Create novel products for the consumer at a sustainable profit

Are expensive enzymes worth the cost?

Biocatalysts (enzymes used as catalysts) let these producers contribute positively to the environment by milder reaction conditions and lower temperatures, while replacing traditional chemical catalysts of considerable toxicity. The obstacle has been in making the new route profitable in the face of high catalyst costs. Bought in small quantities for testing, the US dollar cost is often a five-digit number per kilogram!

How can such an expensive tool be economically viable when used in a process? The answer lies in reusing the enzymes time after time, and thereby spreading the cost over a larger amount of product. The recovery of the biocatalyst at the end of the process is simplified by immobilizing it on a solid support, which is more easily separated from the liquid product than a “free” enzyme would be. However, the immobilized enzymes tend to break under the violent force of a mixer and the gains in separation are offset by the new problem of mechanical damage.

In Biocatalysis engineering: the big picture, Roger Sheldon and Pedro Pereira write “A problem that is often encountered in the use of STRs is mechanical attrition of the immobilised enzyme, resulting from shear forces caused by the propeller stirrer, leading to the formation of pulverised particles which are difficult to separate.”

The solution

SpinChem is determined to catalyze the transformation to sustainable synthesis of chemical products. Seeing the reuse of catalysts as a fundamental challenge in the industry, we invented the rotating bed reactor (RBR) to solve the issue. It has become a game-changer in many fields such as pharmaceuticals, chemicals and the cannabis industry. The RBR protects the immobilized enzymes by retaining them in a unique stirrer equipped with filters. When rotated, the RBR generates a flow of liquid passing the enzymes at a rate superior to that of a column, while completely remediating the issues of attrition associated with a stirred tank reactor.

The rotating bed reactor concept

The proof of the pudding…

…is in the eating! Rotating bed reactors are used by a majority of the biggest pharma companies of 2022 (by revenue). The relevance for production of pharmaceutical ingredients was particularly illustrated by the Medicines For All Institute who developed a new route for manufacturing the antiviral drug Molnupiravir, used for treating Covid-19. The researchers had already managed to decrease the costs substantially from the baseline, but the enzyme use remained high and constituted a whopping 50% of the raw material cost. After implementing an RBR, the damage previously dealt by the stirrer blade was eliminated, and they were able to conveniently reuse the biocatalyst for repeated batches with preserved performance.

AstraZeneca, one of the world's largest pharmaceutical companies, similarly used a SpinChem® rotating bed reactor to improve the recycling of the famous immobilized enzyme Novozym 435. The efforts are published in the esteemed journal Organic Process Research & Development, and the authors note: “We found that the immobilized enzyme was surprisingly stable under these conditions and we could run 10 consecutive recycling experiments with preserved rate of reaction and enantioselectivity of the enzyme”

Pushing the limits even further, a collaboration with ChiralVision B.V. and Purolite Ltd. demonstrated the recycling of an enzyme to 23 full cycles without losses, slicing the catalyst cost by 96%! The production capacity was estimated to 50 kilograms per gram of catalyst thanks to the high catalyst stability.

Enzyme recycling 1019

Get started with biocatalysis

Enzymatic alternatives for the synthesis of chemical products open the door to greener chemistry. Economic challenges have delayed commercial adoption, but now the rotating bed reactor offers an obvious path forward based on immobilized enzymes, used time after time after time. Researchers can now experiment without breaking the bank, and process development scientists can reach the required purity and yield per kilogram of biocatalyst. Chemists can now contribute to a sustainable production of pharmaceuticals.

What is holding you back from benefitting from biocatalysis? Start your rotating bed reactor journey on laboratory scale with a starter kit. Contact us today for a conversation about how SpinChem can serve your needs.