WblA, a Pleiotropic Regulatory Gene Modulating Morphogenesis and Daptomycin Production in Streptomyces Roseosporus

Aims: The wblA gene, encoding a homologue of the WhiB family protein, was identified in the sequenced genome of daptomycin producer Streptomyces roseosporus. To explore the function of wblA, we construct wblA disruption strains, complemented strains and overexpression strains to test whether it can affect the production of secondary metabolites and morphogenesis.

Methods And Results: We constructed disruption strains by homologous recombination in S. roseosporus. The disruption mutant of wblA could block aerial mycelium sporulation and enhance the production of daptomycin by 51%. In contrast, overexpression of wblA resulted in significantly decreased the yield of daptomycin. In agreement with it, the transcription of key daptomycin regulatory genes atrA, dptR2 and dptR3 and structural gene dptE remarkably increased in the wblA disruption mutant.

Conclusions: wblA plays a key role in control of daptomycin biosynthesis and is essential for sporulation. The disruption of wblA could accumulate the transcription level of some key genes involving in daptomycin biosynthesis.

Significance And Impact Of The Study: Daptomycin is an important antibiotic with potent activity against a variety of Gram-positive pathogens. This study demonstrates that valuable improvement in the yield of daptomycin can be achieved through modulating the expression of wblA transcription regulator.