Oxidation reactions can be a challenge for the chemicals industry with concerns about safety, selectivity, side reactions and over oxidations. Codexis is using biocatalysis to overcome these challenges and has recently evolved a novel Baeyer-Villiger monooxygenase (BVMO) enzyme. The enzyme has been optimized for high performance, commercial-scale manufacture of esomeprazole (Nexium®, for the treatment of gastro-esophageal reflux).
BVMO enzymes have originally been studied for their ability to enantioselectively oxidize prochiral ketones to their corresponding esters. More recently we have explored their ability to oxidize prochiral sulfides to the chiral sulfoxides. The BVMO enzyme for the manufacture of esomeprazole was optimized through directed evolution using our CodeEvolver® protein engineering platform.
Traditionally, manufacturing of chiral sulfoxides involves the use of Kagan-Sharpless asymmetric catalysts. This method is laborious, requires auxillaries and peroxides and has a maximum theoretical yield of 50%, so there is a significant yield loss. It is also not perfectly enantioselective, it tends to over oxidize sulfoxides to sulfones leading to yield and purity issues, it typically results in 94% enantiomeric excess.
In contrast to this, using the BVMO enzymes eliminates selectivity issues; they can be evolved to improve activity and enantioselectivity so it also eliminates the side reactions. This method also offers the advantage of using molecular oxygen as the oxygen donor, rather than peroxide, therefore giving a cleaner and typically an easier reaction.
This platform has the potential to be further tuned to various other oxidation reactions of interest in the industry. Pharmaceutical companies can conduct their processing in a more efficient and greener way, giving a cost advantage over metal catalyzed oxidation chemistries.
Find out more about the directed evolution of the BVMO enzymes: http://www.teknoscienze.com/Contents/Riviste/Sfogliatore/CO2_2015/files/assets/basic-html/index.html#52/z#noFlash