Activity-based annotation: the emergence of systems biochemistry

Current tools to annotate protein function have failed to keep pace with the speed of DNA sequencing and exponentially growing number of proteins of un-known function (PUFs). A major contributing factor to this mismatch is the histor-ical lack of high-throughput methods to experimentally determine biochemical activity. Activity-based methods, such as activity-based metabolite and protein profiling, are emerging as new approaches for unbiased, global, biochemical an-notation of protein function. In this review, we highlight recent experimental, activity-based approaches that offer new opportunities to determine protein function in a biologically agnostic and systems-level manner.

Automated summary

Current tools for annotating protein function cannot keep up with the fast pace of DNA sequencing and the exponentially increasing number of proteins with unknown functions. The lack of high-throughput methods for experimentally determining biochemical activity is a major reason for this mismatch. Activity-based methods offer new opportunities for unbiased and comprehensive annotation of protein function.