Milbemycins, a new family of macrolide antibiotics. Fermentation, isolation, physico-chemical properties and bioconversion of milbemycins J and K.

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Abstract
Strain Rf-107, a mutant of Streptomyces hygroscopicus ssp. aureolacrimosus, obtained with UV irradiation, produced 2 new macrolide antibiotics, milbemycins J and K without production of any other milbemycins. Fermentation studies on the strain were conducted in shake flasks and 30 l jar fermentors. Isolation of the antibiotics was performed by adsorption on resinous adsorbent followed by elution with aqueous methanol. Purification of milbemycins J and K was completed with Lobar Si 60 column chromatography to give colorless crystals. Physicochemical data, such as UV, IR and NMR spectra, are described. Milbemycins J and K were readily converted by the intact cells of the parent strain to milbemycins .alpha.1 and .alpha.3, respectively. Physicochemical characterization and the bioconversion studies revealed that milbemycins J and K were new antibiotics having the 16-membered macrocyclic lactone with a 6,6-membered spiroketal ring system.