Discovery of a Potentially New Subfamily of ELFV Dehydrogenases Effective for l-Arginine Deamination by Enzyme Mining.

Abstract

Discovery of enzymes with new functions is very important for de novo pathway design in synthetic biology. Amino acid dehydrogenases catalyze the oxidative deamination of an amino acid to its keto acid, which are widely used for the production of various valuable chemicals. To discover amino acid dehydrogenases with new functions, the authors reevaluate the sequence variability and substrate diversity of ELFV dehydrogenases superfamily in this study. With insights gained from structural and sequential studies, the authors develop an in silico strategy and discover a new category of proteins which are originally annotated as glutamate dehydrogenase but show altered conservation pattern of specificity determined motifs and completely different substrate spectrum. These proteins cannot catalyze the deamination of glutamate and other canonical amino acids except the positively charged amino acid l-arginine, representing a potentially new subfamily of ELFV dehydrogenases. The strategy utilized in this study can also be applied for discovering other useful enzymes.