The inhibition of antibiotic production in Streptomyces coelicolor over-expressing the TetR regulator SCO3201 IS correlated with changes in the lipidome of the strain
2020
Zhang, Jun | Liang, Qiting | Xu, Zhongheng | Cui, Miao | Zhang, Qizhong | Abreu, Sonia | David, Michelle | Lejeune, Clara | Chaminade, Pierre | Virolle, Marie-Joelle | Xu, Delin | Jinan University [Guangzhou] | Lipides : systèmes analytiques et biologiques (Lip(Sys)²) ; Université Paris-Saclay | Institut de Biologie Intégrative de la Cellule (I2BC) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) | Métabolisme Energétique des Streptomyces (MESMIC) ; Département Microbiologie (Dpt Microbio) ; Institut de Biologie Intégrative de la Cellule (I2BC) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) | Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)) ; Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | This work was supported by the National Natural Science Foundation of China (No. 31300046), Guangdong Basic and Applied Basic Research Foundation (Nos. 2019A1515011791 and 2019A1515012112), the Natural Science Foundation of Guangdong Province (No. 2018A030313578), the Science andTechnology Planning Project of Guangdong Province (No.[2019]170) | ANR-17-ASTR-0018,INNOVANTIBIO,MISE EN OEUVRE D UNE STRATEGIE INNOVANTE POUR LA DECOUVERTE DE NOUVEAUX ANTIBIOTIQUES A PARTIR DES BACTERIES STREPTOMYCES(2017)
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Afficher plus [+] Moins [-]anglais. 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.
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