Strain Improvement of a Carbapenem Antibiotic Producer, Streptomyces griseus subsp. cryophilus C-19393, by Protoplast Fusion

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Streptomyces griseus subsp. cryophilus C-19393 produces four unsulfated carbapenem antibiotics (C-19393 H2, E5, and epithienamycins A and B) and their sulfated forms (C-19393 S2, MM 4550, MM 13902 and MM 17880). Predominant accumulation of C-19393 H2 was achieved by using lysine analogue-resistant mutants derived from a sulfate transport-negative mutant, K-4, which produced unsulfated carbapenems only. Highly efficient genetic recombination was successfully performed between the mutants derived from strain C-19393 by polyethylene glycolinduced protoplast fusion. Superior producers of C-19393 S2 were obtained by crossing high producers of C-19393 H2 derived from the sulfate transport-negative mutant, K-4, with the sulfate transport-positive parent. Interspectific recombination was also achieved between the auxotrophs from strain C-19393 and other producers of carbapenem antibiotics.
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