Characterization of varM Encoding Type II ABC Transporter in Streptomyces virginiae, a Virginiamycin M₁ Producer

抄録

Virginiamycin M₁ (VM₁), produced by Streptomyces virginiae, is a polyunsaturated macrolactone antibiotic belonging to the streptogramin family. The 10-kb regulatory gene cluster of VM₁ production contains the varM gene, which encodes the type II ATP-binding cassette (ABC) transporter. This transporter is presumably involved in self-resistance to avoid suicide of the producer strain. Northern blot analyses revealed that varM expression is transcriptionally controlled by the VM₁ molecule, but not by virginiamycin S, which is simultaneously produced to form a synergistic pair of the streptogramin family. Sequential addition of VM₁ at increasing concentrations secured constitutive activation of varM expression, which suggested that the varM expression reflected an intracellular concentration of VM₁. Heterologous expression of varM in Streptomyces lividans generated strains with no significant VM₁ resistance. The mechanism underlying varM function in VM₁ production is discussed.