Sprecher
Beschreibung
Several classes of biological reactions that are mediated by an enzyme-cofactor tandem can also occur without the enzyme and even without the cofactor under catalysis by metal ions – albeit significantly slower [1]. These observations support the idea that precursors to some core metabolic pathways emerged under inorganic catalysis and were later refined by organocatalysis from cofactors and, eventually, by enzymes. Notably, transamination, the biological process by which ammonia is transferred between amino acids and α-keto acids, has been shown to be catalyzed efficiently by metal ions such as Cu2+, Ni2+, Co2+, and V5+, and its mechanism studied in detail [2]. However, in biology this reaction is co-catalyzed by the cofactor pyridoxal phosphate (PLP) and an enzyme, without help from metal ions. To understand how and why the transition from metal catalysis to cofactor catalysis might have taken place, we systematically studied the influence of PLP on a transamination reaction catalyzed by 18 different metals ions. Although PLP was found to substantially accelerate the rate of the Cu2+ and V5+ catalyzed transamination, the largest rate increases came for the two most abundant metals in Earth’s crust, Al3+ and Fe3+, with rate accelerations of 90- and 225-fold, respectively. In the presence of PLP, the reactions co-catalyzed by Al3+ and Fe3+ become competitive with those catalyzed solely by much rarer metal ions such as Cu2+ and V5+. Kinetic and DFT studies performed to probe the mechanism of co-catalysis support a ping-pong mechanism of the reaction. Our results suggest that one of the main reasons for the emergence of PLP in metabolism might have been to allow highly Earth-abundant metals to take over those catalytic functions that were once carried out by less common metals. This trend is not so different from that currently seen in the field of chemical catalysis engineered by humans.
References:
1. a) Wagner, G. R.; Payne, R. M. J Biol Chem 2013, 288 (40), 29036–29045. b) Kirschning, A.. Angewandte Chemie Int Ed 2020, 60 (12), 6242–6269. c) White, H. B. J Mol Evol 1976, 7 (2), 101–104.
2. Mayer, R. J.; Kaur, H.; Rauscher, S. A.; Moran, J. J Am Chem Soc 2021, 143 (45), 19099–19111.
