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

Date Published: March 30, 2017

Publisher: Public Library of Science

Author(s): Lan Yan, Qizhong Zhang, Marie-Joelle Virolle, Delin Xu, Dongsheng Zhou.


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.

Partial Text

Streptomyces are Gram-positive, filamentous soil bacteria of considerable biotechnological importance. Indeed this genus produces two thirds of all known antibiotics as well as other bio-active molecules, including antitumor agents, immune-suppressants, apoptosis inducers and antifungals, herbicides, insecticides etc… used in medicine or agriculture [1]. These bacteria are characterized by a complex developmental cycle that starts, when the nutritional conditions are favorable, by the germination of spores that develop into a substrate mycelium. Subsequently, some still poorly defined signals of nutrient limitation, are thought to trigger the development of aerial hyphae from the substrate mycelium. The tip ends of the aerial hyphae differentiate into uni-genomic spores and the production of a grey pigment encoded by the whiE locus accompanied the complete differentiation process [2,3]. This complex morphological development is mainly under the control of the bld and whi genes, that are required for the formation of aerial mycelium and spores, respectively [2,3].

The WhiB-like transcriptional regulator [35], WblI (SCO5046), studied in this issue was first identified as a target of the transcriptional regulator of the TetR-family (SCO3201). The over-expression of SCO3201 was shown to lead to strong repression of both antibiotic production and sporulation in S. coelicolor [31]. However, since the disruption of SCO3201 did not lead to any obvious phenotype, it was proposed that SCO3201 “illegitimately” governs the expression of target genes normally under the control of other TetR regulators truly involved in the regulation of the differentiation process. It was thus inferred that the analysis of the “SCO3201” targets might lead to the identification of new players in the complex regulation of the differentiation process in S. coelicolor. Indeed, the search for SCO3021 targets allowed the identification of genes already known to be involved in the regulation of the differentiation process, validating this approach, as well as of new players including WblI (SCO5046).




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