IMPROVED ERYTHROMYCIN PRODUCTION IN A GENETICALLY-ENGINEERED INDUSTRIAL STRAIN OF SACCHAROPOLYSPORA-ERYTHRAEA

An industrial erythromycin production strain of Saccharopolyspora eryt hraea spp. was used to demonstrate that careful genetic engineering ca n significantly improve productivity. The chromosomally integrated Vit reoscilla hemoglobin gene (vhb) was shown to enhance the final titer o f erythromycin by some 70% compared to the original S. erythraea spp. Overall, specific erythromycin yields were about 2.5 g of erythromycin /g of total protein for S. erythraea::vhb but <1 for the S. erythraea spp. The maximum rates of biosynthesis were 57.5 mg of erythromycin/(L /h) and 24.3 mg/(L/h) for the recombinant strain S. erythraea::vhb and S. erythraea spp., respectively. Overall space-time yield was 100% hi gher for the S. erythraea::vhb fermentation(1.1 g of erythromycin/(L/d ay)) than for the S. erythraea spp. fermentation (0.56 g of erythromyc in/(L/day)). The genetic stability of the recombinant strain was high, and no selective pressure was needed throughout the cultivations. Exp ression of functional Vitreoscilla hemoglobin throughout the cultivati ons was verified by CO difference spectrum assays.