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Development of a Valuable New Enzyme, Amine Dehydrogenase

First and foremost, pharmaceuticals have to be efficacious, or in other words, they need to work to cure a disease or at least stop its progression. Next, however, pharmaceuticals have to be safe, and last, but not always least, they have to be affordable. Safe pharmaceuticals contain the active ingredient but no impurities. Affordable pharmaceuticals often are those that can be produced with a selective and inexpensive process.

Georgia Tech researchers at the Center for Pharmaceutical Development (CPD) have developed such a process for those pharmaceuticals than contain chiral amines, i.e., nitrogen groups. The FDA requirements around chiral active pharmaceutical ingredients (APIs) have become more stringent in recent years. Chiral molecules are non-superimposable mirror images, like handedness. Of these chiral compounds, chiral amines have had a particularly large and growing demand due to their high biological activity.

The Bommarius Research Team at Georgia Tech has met this demand with the noteworthy development of an amine dehydrogenase to an outstanding level. Not only has the group been successful in modifying an enzyme to produce this activity, but it has gone beyond an “academic” demonstration of this concept to provide an industrial-feasible and suitably applicable level of activity (rate of conversion) with this new enzyme’s capacity.

Multiple versions of this enzyme have been produced, thus creating a new class of enzymes that stand to enable a less expensive process to drug production, and a process with fewer impurities.

Previous methods of producing chiral amines chemically have relied on heavy metals, high-pressure hydrogenation, or crystallization. These operations are costly, hazardous, and not environmentally-friendly.

This breakthrough amine dehydrogenase route is capable of aminating numerous ketones with near perfect selectivity (handedness), making for a more efficient and greener route to produce these compounds. This work presents a viable alternative to the growing class of transaminases. Despite high levels of recognition, including the Presidential Green Chemistry Award, this class of enzymes has substantial disadvantages, such as the cost for the amine and incomplete conversion owing to an unfavorable equilibrium. While these challenges have been met with some level of success, there is a need to produce these chiral amines more efficiently by selective amination of ketones using free ammonia, which has been recognized as one of the most aspired enzymatic reactions previously unavailable by the ACS Pharmaceutical Roundtable. This route allows for increased efficiency and less waste.

This breakthrough has the potential to impact specialty chemicals with a particular emphasis on pharmaceuticals. It will allow for less expensive and more environmentally-friendly routes to chiral amines over the chemical synthesis.

Economic Impact:

The economic impacts of this breakthrough work will be both in cost-savings of production and in decreased use of organic solvents. It will simplify syntheses and creation of higher-quality product compounds. The potential impact is further exemplified by the tremendous interest in this project by center members. The vast majority of CPD member companies have prioritized this project as one of their top interests.

For more information, contact Andreas (Andy) Bommarius at Georgia Tech,, Bio, 404.385.1334.

PDF icon CPD-2016.pdf