The application of natural product inspired synthesis has identified novel antibacterial tetramic acids which exhibit wide ranging antibacterial activity, and which provide potential lead structures for antibacterial drug discovery.Their phenotypic activity appears to correlate with action at two enzymes, UPPS and RNAP, which operate in independent metabolic pathways.SAR maps and identification of their relevant binding sites by mol. modeling has been achieved, and characterization of the most active compounds suggests that these systems offer potential for topical antibiotics but that for oral and injectable use further optimization is required.