Aminotransferases discovery

An additional rare form of RNA is the ribozyme (from nfeonucleic tnzyme). As the name implies, these are RNA molecules that have enzymic activity (Chap. 5). Many ribozymes catalyze the hydrolytic cleavage of RNA of either other RNA molecules or their own RNA. They are also an integral part of ribosomes where they have aminotransferase activity. The discovery of ribozymes, along with the realization that RNA can act as a hereditary molecule, gave rise to the concept by Leslie Orgel of an RNA world this idea posits that in the distant past, simple cells used RNA as structural, catalytic, and genetic elements (see Sec. 1.1). 

Mironov, G.G., St Jacques, A.D., Mungham, A., Eason, M.G., Chica, R.A., Berezovski, M.V. (2013) Bioanalysis for Biocatalysis Multiplexed Capillary Electrophoresis-Mass Spectrometry Assay for Aminotransferase Substrate Discovery and Specificity Profiling. J. Am. Chem. Soc. 135 13728-13736. 

Evdokimov, A., Evrard, E., Fonseca, K.R., Gan, X., Ghosh, S. et al. (2012) Discovery of brain-penetrant, irreversible kynurenine aminotransferase II inhibitors for schizophrenia. ACS Medicinal Chemistry Letters, 3, 187-192. 

Since their discovery, first published by Needham et al, transaminases or aminotransferases (EC2.6.1.X) have received much attention as biocatalysts for the transformation of a keto acid to the corresponding amino acid/amine or vice versa [1]. Transaminases play an important role in amino acid metabolism and are ubiquitous in microbes and eukaryotic cells. They are pyridoxal-5 -phosphate (PLP)-dependent enzymes and are qualified as biocatalysts, due to their wide substrate scope, high enantio- and regioselectivity, high reaction rates, and stability [2]. As pictured in Scheme 29.1, the amino group of the amino donor is transferred to the carbonyl group of the amino acceptor. 

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