Applied techniques for mining natural proteasome inhibitors

► The UPS is the key player in non-lysosomal protein degradation. ► Natural compounds have been optimized during evolution and implement lead structure motives for drug development. ► The intersection of methodologies permits the discovery of novel leads. ► Induction of natural product biosynthesis is triggered by distinct molecular environments. ► The natural product family of syrbactins and their biological functions during pathogenesis