S68: Identification of Proteins Relevant to Bioenergy and Fungal Disease Pathology by Chemical Proteome Profiling

A complex and highly challenging research objective is the identification of proteins linked to cellular functions, and the characterization of the small molecule and protein interactions and modifications that facilitate cellular functions and regulate key pathways in living systems. In response to this fundamental challenge we have developed an integrated chemical proteomics platform for quantitatively measuring functionally active enzymes, small molecule-protein interactions, post-translational modifications, and protein-protein interactions using a multiplexed chemical probe approach. The development of this chemical proteomics platform has required the synthesis of several small molecule chemical probes for interrogating proteomes for functions, modifications, and interactions of interest. This research is providing value for current systems biology and functional genome annotation efforts, and yielding data previously unattainable. Importantly, the new chemical proteome profiling approach is broadly applicable to diverse research areas. We have employed our methodology on two primary foci: (1) identifying functionally active enzymes from the thermophilic fungus, Thielavia terrestris, involved in the degradation of lignocellulose, and (2) understanding key proteolytic pathways and functions in a fungal lung pathogen, Aspergillus fumigatus. Our chemical proteome profiling efforts are providing key insights into both bioenergy and disease pathology research.