Antibiotic GE37468A: a new inhibitor of bacterial protein synthesis. III. Strain and fermentation study

GE37468A is a new thiazolyl peptide antibiotic acting on Elongation Factor Tu, produced by fermentation of Streptomyces sp. ATCC 55365. The low (< 10 mg/liter) and poorly reproducible antibiotic productivity of the original soil isolate hampered the development of a scalable fermentation process. A tenfold increase of GE37468A productivity was achieved by selection of spontaneous morphochromatic variants, which appeared at high frequency in the wild type population. The higher producing ATCC 55365/O/5 colony was tyrosinase defective and blocked in the aerial mycelium differentiation (Amy-Mel- phenotype). The fermentation process of this stable and purified strain was rapidly optimized to achieve a further fourfold improvement in a fed-batch process.