BIOSYNTHESIS OF THIOPEPTIDE ANTIBIOTIC A10255 IN STIRRED REACTORS USING A CHEMICALLY DEFINED MEDIUM SUPPLEMENTED WITH CONTINUOUS NUTRIENT FEEDS

A10255 is a complex of new thiopeptide antibiotics produced by Streptomyces gardneri. When stirred reactors were operated in batch mode using a defined medium with a glucose feed, 250-mu-g/ml of A10255 were produced during a four-day fermentation cycle. The linear growth phase of S. gardneri was extended through seven days by supplementing the defined medium with continuous feeds of hydrolyzed casein and methyl caprate. With the supplementary feeds, antibiotic biosynthesis paralleled growth during the extended cycle and attained levels of 1,750-mu-g/ml. Increasing the standard glucose feed rate increased titers principally by increasing cell mass. Supplementing the standard glucose feed with lipids such as caprylate or caprate, and decyl alcohol, affected cell mass minimally but produced higher titers by increasing the specific biosynthesis of A10255 per unit of biomass.