Catalysis

Enzymes that improve the production of Atorvastatin calcium, an essential building block of Lipitor. Atorvastatin calcium is produced through hydroxynitrile (HN). This conventional process yields less than 50% and requires hydrogen bromide (a hazardous chemical). Codexis introduces a new enzymatic pathway that consists of three bioengineered enzymes that reduce the original process to two steps. This new process by Codexis® works in mild conditions and produces significantly higher yields. It also reduces environmental and health hazards by producing fewer byproducts and waste.

Synthesis of sitagliptin for drug, Januvia, developed through a collaboration between Merck & Co., Inc. and Codexis, Inc. Januvia is used to treat type II diabetes. The active ingredient, sitagliptin, conventionally requires an expensive and energy-intensive crystallization and high-pressure step. These companies use transaminase enzymes to increase selectivity and efficiency and reduce overall waste. 

Four-step synthetic route for ibuprofen production. This company's four-step synthetic route is an alternative to the traditional six-step synthetic route. This new process has 90% atom efficiency compared to the original process with less than 40% atom efficiency. Using anhydrous hydrogen fluoride as a solvent and catalyst reduces the volume of generated waste and increases the reaction's selectivity. Anhydrous hydrogen can also be recovered and reused with 99.9% efficiency.

Improved synthesis of aprepitant, the active ingredient in Emend® — a drug that combats chemotherapy-induced nausea and vomiting. This new process assembles aprepitant in 3 highly atom-economical steps (compared to the traditional 6 steps) and nearly doubles the yield. Compared with the first-generation synthesis, this new route eliminates sodium cyanide, dimethyl titanocene, and gaseous ammonia. This new process also requires only 20% of the raw materials and water used in the original process, eliminating approximately 41,000 gallons of waste per 1,000 pounds of aprepitant.

Improved synthesis of Prevymis™, a prescription medicine that helps prevent cytomegalovirus (CMV) infection and disease in adults who have received bone marrow transplants. This antiviral drug uses an improved chemical catalyst, increases the overall yield by 60%, reduces the PMI by 73%, reduces raw material costs by 93%, and reduces water usage by 90%. Merk claims this synthesis will result in the elimination of over 15,000 MT of waste over its lifetime. It should also decrease the product's carbon footprint and water usage by 89% and 90%, respectively.

Solid catalyst alkylation process for the production of alkylate. Alkylate is a clean fuel component of gasoline. Traditional production methods use toxic liquid acid technologies that require post-treatment. Using the Alkystar catalyst, AlkyClean is a more efficeint alkylate production process that increases reaction speed and reduces environmental hazards by eliminating the need for liquid acids.

Highly magnetic materials for enzyme immobilization. Enzyme immobilization can improve enzyme stability and enable enzyme recycling. This company uses a highly magnetic matrix that protects the enzymes from degradation and denaturation, allowing them to function in more extreme temperatures and pHs. The immobilized enzymes are also optimized to reach full activity and high loadings. The magnetic matrix allows the enzymes to easily and quickly recover with a simple magnet. This technology allows for cost-effective, industrial biocatalysis with better activity, results, and productivity.

Custom-designed industrial enzymes. Zymvol® designs custom enzymes for applications in pharmaceutical, chemical, and biotech industries using Zymvol® Biomodeling SL. Zymvol® Biomodeling SL uses cloud-based computer simulations to improve the performance of enzymes to meet precise industrial requirements. Silico evolution technology is used to accelerate protein optimization and reduce costs. Tailoring enzymes through simulations reduces reagent waste. Biocatalysts also contribute to efficient resource use of energy, water, and manufacturing inputs as well as reduce gas emissions.

First-generation surface display technology for better performing enzymes. This technology allows enzymes to be displayed on the outer membrane of bacteria, generating faster results in the screening of binding partners, inhibitors, and optimized enzymes. This technology makes the purification of enzymes simpler and cheaper as it only requires centrifugation and filtration. 

Bioprocesses for chemical manufacturing. The Biochemize (P2B) technological platform is a more profitable, non-hazardous, and low-waste alternative to synthetic chemical manufacturing processes. Bioprocesses are highly selective and efficient. Enzymes used in bioprocesses are efficient and can be reused several times, reducing waste. Bioprocesses also reduce energy usage by enabling reactions to occur in mild or moderate conditions. Reagents and reaction conditions in bioprocessing are also less dangerous.