Biology

Frank M. Raushel
Texas A&M University, College Station, Texas

The rate at which new genes are being sequenced greatly exceeds our ability to correctly annotate the functional properties of the corresponding proteins. Annotations based primarily on sequence identity to experimentally characterized proteins are often misleading because closely related sequences can have different functions, while highly divergent sequences may have identical functions.  Our understanding of the principles that dictate the catalytic properties of enzymes, based on protein sequence alone, is often insufficient to correctly annotate proteins of unknown function.  New methods must therefore be developed to define the sequence boundaries for a given catalytic activity and new approaches must be formulated to identify those proteins that are functionally distinct from their close sequence homologues.  To address these problems, we are working to develop a comprehensive strategy for the functional annotation of newly sequenced genes using a combination of structural biology, bioinformatics, computational biology, and molecular enzymology.  The power of this approach for discovering new reactions catalyzed by uncharacterized enzymes is being tested using the amidohydrolase superfamily (AHS) as a model system.  In this presentation we will describe the discovery of new enzyme activities that are specific for the deamination of 5-methylcytosine and cyclic-3’-5’-AMP, the two-step hydrolysis of ribose-5-phosphate-1,2-cyclic phosphate, and a novel metabolic pathway for L-galactose in Bacteroides vulgatus from the human microbiome.