Genomic Enzymology: Web Tools for Leveraging ProteinFamily Sequence–Function Space and Genome Context to DiscoverNovel Functions

摘要

The exponentially increasing number of protein and nucleic acid sequences provides opportunities to discover novel enzymes, metabolic pathways, and metabolitesatural products, thereby adding to our knowledge of biochemistry and biology. The challenge has evolved from generating sequence information to mining the databases to integrating and leveraging the available information, i.e., the availability of “genomic enzymology” web tools. Web tools that allow identification of biosynthetic gene clusters are widely used by the natural products/synthetic biology community, thereby facilitating the discovery of novel natural products and the enzymes responsible for their biosynthesis. However, many novel enzymes with interesting mechanisms participate in uncharacterized small-molecule metabolic pathways; their discovery and functional characterization also can be accomplished by leveraging information in protein and nucleic acid databases. This Perspective focuses on two genomic enzymology web tools that assist the discovery novel metabolic pathways: (1) EnzymeFunction Initiative-Enzyme Similarity Tool (EFI-EST) for generatingsequence similarity networks to visualize and analyze sequence–functionspace in protein families and (2) Enzyme Function Initiative-GenomeNeighborhood Tool (EFI-GNT) for generating genome neighborhood networksto visualize and analyze the genome context in microbial and fungalgenomes. Both tools have been adapted to other applications to facilitatetarget selection for enzyme discovery and functional characterization.As the natural products community has demonstrated, the enzymologycommunity needs to embrace the essential role of web tools that allowthe protein and genome sequence databases to be leveraged for novelinsights into enzymological problems.