Viewing the human microbiome through three-dimensional glasses: integrating structural and functional studies to better define the properties of myriad carbohydrate-active enzymes

Abstract

Recent studies have provided an unprecedented view of the trillions of microbes associated with the human body. The human microbiome harbors tremendous diversity at multiple levels: the species that colonize each individual and each body habitat; the genes that are found in each organism's genome; the expression of these genes and the interactions and activities of their protein products. The sources of this diversity are wide-ranging and reflect both environmental and host factors. A major challenge moving forward is defining the precise functions of members of various families of proteins represented in our microbiomes, including the highly diverse carbohydrate-active enzymes (CAZymes) involved in numerous biologically important chemical transformations, such as the degradation of complex dietary polysaccharides. Coupling metagenomic analyses to structural genomics initiatives and to biochemical and other functional assays of CAZymes will be essential for determining how these as well as other microbiome-encoded proteins operate to shape the properties of microbial communities and their human hosts.

Figure 1

CAZymes are modular and increasingly described only by high-throughput sequencing data. (a) Growth of sequence, functional and structural data in the CAZy database. (b) Example of modular variation in CAZymes containing a common CBM10 domain.