Masahiko Yoneda

Ansamitocin, a group of novel maytansinoid antibiotics with antitumour properties from Nocardia

WE have isolated a new group of ansamycin antibiotics with potent antitumour activity, from a fermentation broth of Nocardia sp. No. C-15003 (N-l) and have named it ansamitocin. Structures of ansamitocin were found to be similar to maytansine and related maytansinoids obtained from plant sources by Kupchan et al.1–4 and Wani et al.5. These comounds have strong antitumour activities, but development of production would be difficult, because plants containing maytansinoids are only harvested in tropical areas and their content in the plants is extremely low. Some attempts have been made to find a maytansinoid-producing microorganism6, but no success has been reported. We report here the microbial production, isolation and structural elucidation of these antibiotics and their antitumour activities against several experimental tumours in mice.

Motile Actinomycetes: Actinosynnema pretiosum subsp. pretiosum sp. nov., subsp. nov., and Actinosynnema pretiosum subsp. auranticum subsp. nov.

Three strains of motile nocardioform actinomycetes were isolated from sedge blades. The characteristics of these isolates led us to assign them to the genus Actinosynnema. Accordingly, we propose the following new taxa of Actinosynnema: Actinosynnema pretiosum subsp. pretiosum sp. nov., subsp. nov., containing type strain C-15003(N-1) (= IFO 13726 = FERM-P 3992 = ATCC 31281) and strain C-14919(N-2001) (= IFO 13723 = FERM-P 3991 = ATCC 31280); and Actinosynnema pretiosum subsp. auranticum subsp. nov., with type strain C-14482(N-1001) (= IFO 13725 = FERM-P 4130 = ATCC 31309).

Inhibition of Cilia Regeneration of Tetrahymena by Ansamitocins, New Antitumor Antibiotics

Ansamitocins inhibited cilia regeneration of partially deciliated Tetrahymena pyriformis W, and the activity depended on the acyl groups at the C3 position.

Ansamitocin-induced Synchrony in Tetrahymena pyriformis

Ansamitocins inhibited cell division in Tetrahymena pyriformis W at low concentrations and caused cells to become more rounded. Exposure to ansamitocins for 5 h or more resulted in a burst of synchronous division at 100 min after removal of the antibiotics with a maximum division index of 70%. A second burst of synchronous division occurred 300 min after removal with a peak division index of 55%. The rounding of the cell shape was restored by the completion of the first division. When RNA or protein synthesis was blocked by chromomycin A3 or cycloheximide, the first division was suppressed. When DNA synthesis was blocked by methotrexate plus uridine, synchronous division still occurred; furthermore, the DNA content of T. pyriformis cells did not increase before the first division. These findings suggests that the first synchronous division requires RNA and protein synthesis but does not require DNA synthesis. Interference by ansamitocins with the fuction of microtubule systems in T. pyriformis is discussed.