Milbemycins, a new family of macrolide antibiotics. Fermentation, isolation and physico-chemical properties of milbemycins D,E,F,G and H.

Strain Au-3, a mutant of Streptomyces hygroscopicus subsp. aureolacrimosus, obtained with ultraviolet irradiation, was a high-yield strain of milbemycins D, E, F, G and H. Fermentation studies on the strains were conducted in shake flasks and 30-liter jar fermentors. Isolation of the metabolites was performed by adsorption on resinous adsorbent followed by elution with aqueous MeOH and separated by silica gel column chromatography. Milbemycin D was obtained as colorless needles after recrystallization and milbemycins E, F, G and H were purified to homogeneity by column chromatography. Physico-chemical characterization revealed that milbemycins D, E, F, G and H were new antibiotics possessing the 16-membered macrocyclic lactone with a 6,6-membered spiroketal ring system.