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32 PROCEEDINGS OF INTERNATIONAL SCIENTIFIC CONFERENCE ON APPLIED BIOTECHNOLOGYTable 2. Activity spectrum of Ecumicin.4. DISCUSSIONThe discovery of ecumicindemonstrates that new potent antiTB secondary metabolites may be uncovered from actinomycetes by direct whole-cell based high-throughput screening. An orthogonal set of fractionation methods and an extensive panel of analytical methods led to the structural characterization of this relatively high-MW natural product. The ability of ecumicin to maintain its high potency against M .tuberculosis H37Rv-isogenic strains that are monoresistant to rifampin, streptomycin and cycloserine, suggests that ecumicin has a different molecular target from these drugs. Genome mining of lab-generated, spontaneous ecumicin-resistant M. tuberculosis identified the ClpC1 ATPase complex as the putative target, and this was confirmed by a drug affinity response test. Complete inhibition of M. tuberculosis growth by ecumicin was achieved in a mouse