Abstract
In condition of over-expression, SCO3201, a regulator of the TetR family was previously shown to strongly inhibit antibiotic production and morphological differentiation in Streptomyces coelicolor M145. In order to elucidate the molecular processes underlying this interesting, but poorly understood phenomenon, a comparative analysis of the lipidomes and transcriptomes of the strain over-expressing sco3201 and of the control strain containing the empty plasmid, was carried out. This study revealed that the strain over-expressing sco3201 had a higher triacylglycerol content and a lower phospholipids content than the control strain. This was correlated with up- and down- regulation of some genes involved in fatty acids biosynthesis (fab) and degradation (fad) respectively, indicating a direct or indirect control of the expression of these genes by SCO3201. In some instances, indirect control might involve TetR regulators, whose encoding genes present in close vicinity of genes involved in lipid metabolism, were shown to be differentially expressed in the two strains. Direct interaction of purified His6-SCO3201 with the promoter regions of four of such TetR regulators encoding genes (sco0116, sco0430, sco4167, and sco6792) was demonstrated. Furthermore, fasR (sco2386), encoding the activator of the main fatty acid biosynthetic operon, sco2386-sco2390, has been shown to be an illegitimate positive regulatory target of SCO3201. Altogether our data demonstrated that the sco3201 over-expressing strain accumulates TAG and suggested that degradation of fatty acids was reduced in this strain. This is expected to result into a reduced acetyl-CoA availability that would impair antibiotic biosynthesis either directly or indirectly.
Highlights
Streptomyces are Gram-positive filamentous bacteria living in terrestrial, marine and fresh water ecosystems where they play essential biological roles
Since a putative negative correlation between antibiotics biosynthesis and triacylglycerol family (TAG) content was previously reported (Le Marechal et al, 2013; Esnault et al, 2017), we mainly examined the consequences of sco3201 over-expression on fatty acid metabolism
Since our previous results indicated the existence of a negative correlation between TAG content and antibiotic biosynthesis (Le Marechal et al, 2013; Esnault et al, 2017), analysis of the lipid content of M145/pWHM3 and M145/pWHM3sco3201 was carried out using LC/Corona-CAD (Abreu et al, 2017)
Summary
Streptomyces are Gram-positive filamentous bacteria living in terrestrial, marine and fresh water ecosystems where they play essential biological roles (van der Meij et al, 2017). Regulatory cascades triggered by the sensing of extracellular and/or intracellular signals are involved in the control of the developmental program (Pereira et al, 2011) These include Ser/Thr/Tyr eukaryoticlike protein kinases or phosphatases (Petrickova and Petricek, 2003; Pereira et al, 2011), membrane-anchored sensory Histidine kinases from two-component systems (Rodriguez et al, 2013), as well as transcriptional regulators able to interact with specific ligands (Romero-Rodriguez et al, 2015). The ability of SCO3201 to control the expression of numerous “illegitimate” targets was attributed to the presence of a long
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