Heterologous expression of a putative K+/H+ antiporter of S. coelicolor A3(2) enhances K+, acidic-pH shock tolerances, and geldanamycin secretion.

Heterologous expression of a putative K+/H+ antiporter of Streptomyces coelicolor A3(2) (designated as sha4) in E. coli and Streptomyces hygroscopicus JCM4427 showed enhanced tolerance to K+ stress, acidic-pH shock, and/or geldanamycin production under K+ stress. In a series of K+ extrusion experiments with sha4-carrying E. coli deficient in the K+/H+ antiporter, a restoration of impaired K+ extrusion activity was observed. Based on this, it was concluded that sha4 was a true K+/H+ antiporter. In different sets of experiments, the sha4-carrying E. coli showed significantly improved tolerances to K+ stresses and acidic-pH shock, whereas sha4-carrying S. hygroscopicus showed an improvement in K+ stress tolerance only. The sha4-carrying S. hygroscopicus showed much higher geldanamycin productivity than the control under K+ stress condition. In another set of experiments with a production medium, the secretion of geldanamycin was also significantly enhanced by the expression of sha4.