Selective Accumulation of Unsulfated Carbapenem Antibioticsby Sulfate Transport-negative Mutants ofStreptomycesgriseussubsp.cryophilusC-19393

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Abstract
Sulfate transport-negative mutants were derived from Streptomyces griseus subsp. cryophilus C-19393 which coproduced sulfated and unsulfated carbapenem antibiotics. These mutants were successfully obtained by two approaches: (1) the requirement of thiosulfate or l-cysteine for growth and (2) resistance to selenate. The sulfate transport-negative mutants selectively produced unsulfated carbapenem antibiotics and the titers were almost equivalent to the sum of the titers of the sulfated and unsulfated carbapenems produced by the parent. The characterization of the sulfate transport system and sulfur metabolism in Streptomyces are also described.