Highlighting Biocatalysis Trends & Innovation from a Patent Literature 

Biocatalysis is now a well-established technology for the industrial production of fine chemicals. Also, in recent years, a slew of chemical firms have embraced biocatalysis for the production of chemicals. In this insight, the examples are in accordance with the general trend that it is the mature enzyme classes that we see immobilization of, such as the examples of lipases and aldolases.

In a recent paper, D. L. Hughes reviews and summarizes trends and innovations in biocatalysis in the patent literature since 2018. At SpinChem, we like to take the opportunity to highlight the patent examples using immobilized enzymes a little extra.

  • Case 1: An example of direct conversion of acids and esters to amides catalyzed by lipases. In this literature a group from Thermo Fischer Scientific demonstrated the amidation with and immobilized CalB in MTBE, 1,4-dioxane, diisopropyl ether, and 2-methyl-2-butanol. Here, due to the limited solubility of amino acids in organic solvents, the direct amidation of amino acids with ammonia was not reported.

  • Case 2: The direct amidation of a diester pharmaceutical intermediate was described by a Pfizer team as another example. There are a few noteworthy aspects of the results. As per the results the reaction did not work with soluble lipase but worked well with several immobilized formulations demonstrating the stabilization that is possible by immobilization. This may be especially important for reactions in organic media. The use of hexamethyldisilazane (HMDS) as a sort of ammonia as a first. The reaction was carried out up to a scale of 110 kg, serving as an illustration of how biocatalysis is increasingly being used in pilot and production scale pharmaceutical manufacturing.

  • Case 3: An illustration of an early biocatalytic reaction that forms carbon-carbon bonds. While lipases were demonstrated to catalyze aldol reactions in 2003 (Hult, Berglund et al.), in 2020 a research group developed the concept to involve three-component chromene-forming reactions. A variety of aldehydes produced products in the three-component reaction in the 97-99% range with high enzyme loadings. The enzyme retained high activity for five re-uses.

  • Case 4: One more example of L-threonine aldolases that catalyzes the retro-aldol of threonine to glycine and acetaldehyde. As per author several patents now report on catalysis by engineered L-threonine aldolase (LTA) in the synthesis direction for the production of aryl b-hydroxy-a-amino acids from benzaldehyde and glycine. A remarkable number of uses were demonstrated for the reaction.

Here are some applications of RBR using Lipases:

RBR-Jul-07-2022-04-09-41-37-PMThe RBR makes the process fast and simple, provides efficient sampling and monitoring of the process without filtration steps and keeps the immobilized catalyst safely confined inside the rotating bed reactor.

Interested in the rotating bed reactor? Let SpinChem help you understand how the rotating bed reactor technology can simplify or improve your process. Get in touch with us today to get started towards better, more efficient biocatalysis.

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