Aug 25 – 27, 2021
Europe/Berlin timezone

Mechanistic Insight into Metal Ion-Catalyzed Transamination Under Biological Conditions and its Evolutionary Implications

Aug 25, 2021, 3:00 PM


Due to unstable situation with Covid-19 the event will be held online!


Joseph Moran (University of Strasbourg)


Several classes of biological reactions that are mediated by an enzyme and a co-factor can occur, to a slower extent, not only without the enzyme but even without the co-factor, under catalysis by metal ions. This observation has led to the proposal that metabolic pathways progressively evolved from using inorganic catalysts to using organocatalysts of increasing complexity. However, there is no clear example for which all three levels of catalytic complexity are demonstrated and mechanistically understood under biological conditions. Transamination, the biological process by which ammonia is transferred between amino acids and ketoacids, has a mechanism that has been well studied under enzyme/co-factor catalysis and under co-factor catalysis, but the metal ion-catalyzed variant was generally studied mostly at high temperatures (70-100 ºC) and the details of its mechanism remain unclear. Here, we investigate which metal ions catalyze transamination under conditions relevant to biology (pH 7, 20-50 ºC) and study the mechanism in detail. Cu2+, Ni2+, Co2+ and V5+ were identified as the most active metal ions under these constraints. Kinetic, stereochemical and computational studies illuminate the mechanism of the reaction. Cu2+ and Co2+ are found to predominantly speed up the reaction by stabilizing a key imine intermediate. V5+ is found to predominantly accelerate the reaction by increasing the acidity of the bound imine. Ni2+ is found to do both to a limited extent. A mechanistic continuity across levels of catalytic complexity is revealed which could have facilitated a smooth transition during the evolution of biochemistry from transamination catalyzed by metals, to one catalyzed by a co-factor, pyridoxal phosphate (PLP), and eventually to one catalyzed by both PLP and enzymes. Examining other biological reactions in this way may provide a systematic approach to understanding the co-evolution of co-factors and metabolism.

Presentation materials

There are no materials yet.