Isolation, Structural Elucidation, Biological Properties, and Biosynthesis of Maleimycin, a New Bicyclic Maleimide Antibiotic Isolated from the Culture Filtrates of Streptomyces showdoensis

Maleimycin is a bicyclic maleimide antibiotic elaborated by Streptomyces showdoensis. The physical and chemical data show the structure for maleimycin to be 3-aza-6-hydroxybicyclo[3.3.0]oct-Δ1,5-ene-2,4-dione. The nuclear magnetic resonance (nmr) spectra in D₂O showed five well-defined resonances corresponding to the five nonexchangeable protons. The 13C spectra consisted of seven resonances: two resonances in the carbonyl region at –41.3 and –40.7 ppm, two resonances in the aromatic or unsaturated region at – 29.3 and –23.7 ppm, and one resonance at +56.3 ppm corresponding to the carbinol carbon and two saturated carbons at +95.1 and +103.9 ppm. Maleimycin is an effective inhibitor of Gram-positive, Gram-negative, and acid-fast bacteria and leukemia L-1210 cells. Maleimycin reacts more slowly with cysteine or with the sulfhydryl groups of guanosine-5′-triphosphate 8-formylhydrolase at equimolar concentrations. The biosynthesis of the maleimide ring of maleimycin differs from the biosynthesis of showdomycin even though both compounds have the maleimide ring and are synthesized at the same time by the same organism.