<jats:title>Abstract</jats:title><jats:p>Two novel antibiotics, thuggacin A (<jats:bold>1</jats:bold>) and B (<jats:bold>2</jats:bold>), were isolated from the myxobacterium<jats:italic>Sorangium cellulosum</jats:italic>.<jats:bold>1</jats:bold>and<jats:bold>2</jats:bold>are unique thiazole‐containing macrolides with side chains on both sides of the lactone group. Upon standing in solution, thuggacin A (<jats:bold>1</jats:bold>) rearranges by acyl migration of the lactone group to give a mixture with thuggacins B (<jats:bold>2</jats:bold>) and C (<jats:bold>3</jats:bold>). NOEs and vicinal coupling constants within the lactone ring provided distinct data for the generation of a structure model by PM3 calculations, which allowed an analysis of the conformation in solution and the relative configuration of six asymmetric centres. A minor sorangium metabolite was identified as 13‐methyl‐thuggacin A (<jats:bold>4</jats:bold>). Furthermore, two natural thuggacin variants,<jats:bold>5</jats:bold>and<jats:bold>6</jats:bold>, were found in another myxobacterium,<jats:italic>Chondromyces crocatus</jats:italic>. In these variants, one side chain is replaced by a methyl group and a hydroxy group is repositioned to give a primary alcohol at the former methyl site, in an α position with respect to the thiazole ring.<jats:bold>1</jats:bold>proved to be active against clinical isolates and reference strains of<jats:italic>Mycobacterium tuberculosis.</jats:italic>Preliminary studies on the mechanism of action indicate inhibition of the cellular electron‐transport chain.