The TetR family of regulators are an important group of transcription regulators that regulate diverse cellular processes in prokaryotes.In this study,we found that XNR_0706,a TetR family regulator,controlled the expr...The TetR family of regulators are an important group of transcription regulators that regulate diverse cellular processes in prokaryotes.In this study,we found that XNR_0706,a TetR family regulator,controlled the expression of XNR_0345,XNR_0454,XNR_0513 and XNR_1438 putatively involved in fatty acidβ-oxidation by interacting with the promoter regions in Streptomyces albus B4.The transcription level of these four genes was downregulated in XNR_0706 deletion strain(ΔXNR_0706)and restored by XNR_0706 complementation inΔ0706/pIB-0706,demonstrating that XNR_0706 was a positive transcriptional regulator of the genes.With toxic long-chain fatty acids addition in TSB media,deletion of XNR_0706 caused significantly poor growth,whereas XNR_0706 complementation increased the utilization of additional fatty acids,resulting in restored growth.Fatty acidβ-oxidation is one source of acetyl-and malonyl-CoA precursors for polyketides biosynthesis in actino-bacteria.Overexpression of XNR_0706 in B4/spnNEW,a spinosad heterologous expression strain derived from S.albus B4,increased spinosad yield by 20.6%.Additionally,supplement of 0.3 g/L fatty acids resulted in a further 42.4%increase in spinosad yield.Our study reveals a regulatory mechanism in long-chain fatty acids metabolism in S.albus and these insights into the molecular regulation ofβ-oxidation by XNR_0706 are instrumental for increasing secondary metabolites in actinobacteria.展开更多
The microbial genome remains a huge treasure trove for the discovery of diverse natural products.Saccharopolyspora erythraea NRRL23338,the industry producer of erythromycin,has a dozen of biosynthetic gene clusters wh...The microbial genome remains a huge treasure trove for the discovery of diverse natural products.Saccharopolyspora erythraea NRRL23338,the industry producer of erythromycin,has a dozen of biosynthetic gene clusters whose encoding products are unidentified.Heterologous expression of one of the polyketide clusters pks7 in Streptomyces albus B4 chassis resulted in the characterization of its function responsible for synthesizing both 6-methylsalicyclic acid and 6-ethylsalicyclic acid.Meanwhile,two new 6-ethylsalicyclic acid ester derivatives were isolated as shunt metabolites.Their structures were identified by comprehensive analysis of MS and NMR experiments.Putative functions of genes within the pks7 BGC were also discussed.展开更多
基金support from the National Key Research and Development Program of China(No.2018YFA0900404).
文摘The TetR family of regulators are an important group of transcription regulators that regulate diverse cellular processes in prokaryotes.In this study,we found that XNR_0706,a TetR family regulator,controlled the expression of XNR_0345,XNR_0454,XNR_0513 and XNR_1438 putatively involved in fatty acidβ-oxidation by interacting with the promoter regions in Streptomyces albus B4.The transcription level of these four genes was downregulated in XNR_0706 deletion strain(ΔXNR_0706)and restored by XNR_0706 complementation inΔ0706/pIB-0706,demonstrating that XNR_0706 was a positive transcriptional regulator of the genes.With toxic long-chain fatty acids addition in TSB media,deletion of XNR_0706 caused significantly poor growth,whereas XNR_0706 complementation increased the utilization of additional fatty acids,resulting in restored growth.Fatty acidβ-oxidation is one source of acetyl-and malonyl-CoA precursors for polyketides biosynthesis in actino-bacteria.Overexpression of XNR_0706 in B4/spnNEW,a spinosad heterologous expression strain derived from S.albus B4,increased spinosad yield by 20.6%.Additionally,supplement of 0.3 g/L fatty acids resulted in a further 42.4%increase in spinosad yield.Our study reveals a regulatory mechanism in long-chain fatty acids metabolism in S.albus and these insights into the molecular regulation ofβ-oxidation by XNR_0706 are instrumental for increasing secondary metabolites in actinobacteria.
基金support from the National Key Research and Development Program of China(Nos.2018YFA0900404 and 2022YFC2804105)the National Natural Science Foundation of China(No.82273849).
文摘The microbial genome remains a huge treasure trove for the discovery of diverse natural products.Saccharopolyspora erythraea NRRL23338,the industry producer of erythromycin,has a dozen of biosynthetic gene clusters whose encoding products are unidentified.Heterologous expression of one of the polyketide clusters pks7 in Streptomyces albus B4 chassis resulted in the characterization of its function responsible for synthesizing both 6-methylsalicyclic acid and 6-ethylsalicyclic acid.Meanwhile,two new 6-ethylsalicyclic acid ester derivatives were isolated as shunt metabolites.Their structures were identified by comprehensive analysis of MS and NMR experiments.Putative functions of genes within the pks7 BGC were also discussed.
