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Regulators of the WhiB-like ( wbl ) family are playing important role in the complex regulation of metabolic and morphological differentiation in  Streptomyces . In this study, we investigated the role of  wblI , a member of this family, in the regulation of secondary metabolite production in  Streptomyces lividans . The over-expression of  wblI  was correlated with an enhanced biosynthesis of undecylprodigiosin and actinorhodin and with a reduction of the biosynthesis of yCPK and of the grey spore pigment encoded by the  whiE  locus. Five regulatory targets of WblI were identified using  in vitro  formaldehyde crosslinking and confirmed by EMSA and qRT-PCR. These included the promoter regions of  wblI  itself, two genes of the ACT cluster ( actVA3  and the intergenic region between the divergently orientated genes  actII-1  and  actII-2 ) and that of  wblA , another member of the Wbl family. Quantitative RT-PCR analysis indicated that the expression of  actVA3  encoding a protein of unknown function as well as that of  actII-1 , a TetR regulator repressing the expression of  actII-2 , encoding the ACT transporter, were down regulated in the WblI over-expressing strain. Consistently the expression of the transporter  actII-2  was up-regulated. The expression of WblA, that is known to have a negative impact on ACT biosynthesis, was strongly down regulated in the WblI over-expressing strain. These data are consistent with the positive impact that WblI over-expression has on ACT biosynthesis. The latter might result from direct activation of ACT biosynthesis and export and from repression of the expression of WblA, a likely indirect, repressor of ACT biosynthesis.

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In conditions of over-expression, WblI, a WhiB-like transcriptional regulator, has a positive impact on the weak antibiotic production of Streptomyces lividans TK24