Dataset Information

Combinatorial Effect of ARTP Mutagenesis and Ribosome Engineering on an Industrial Strain of Streptomyces albus S12 for Enhanced Biosynthesis of Salinomycin.

ABSTRACT: Salinomycin, an important polyketide, has been widely utilized in agriculture to inhibit growth of pathogenic bacteria. In addition, salinomycin has great potential in treatment of cancer cells. Due to inherited characteristics and beneficial potential, its demand is also inclining. Therefore, there is an urgent need to increase the current high demand of salinomycin. In order to obtain a high-yield mutant strain of salinomycin, the present work has developed an efficient breeding process of Streptomyces albus by using atmospheric and room temperature plasma (ARTP) combined with ribosome engineering. In this study, we investigate the presented method as it has the advantage of significantly shortening mutant screening duration by using an agar block diffusion method, as compared to other traditional strain breeding methods. As a result, the obtained mutant Tet30Chl25 with tetracycline and chloramphenicol resistance provided a salinomycin yield of 34,712 mg/L in shake flask culture, which was over 2.0-fold the parental strain S12. In addition, comparative transcriptome analysis of low and high yield mutants, and a parental strain revealed the mechanistic insight of biosynthesis pathways, in which metabolic pathways including butanoate metabolism, starch and sucrose metabolism and glyoxylate metabolism were closely associated with salinomycin biosynthesis. Moreover, we also confirmed that enhanced flux of glyoxylate metabolism via overexpression gene of isocitrate lyase (icl) promoted salinomycin biosynthesis. Based on these results, it has been successfully verified that the overexpression of crotonyl-CoA reductase gene (crr) and transcriptional regulator genes (orf 3 and orf 15), located in salinomycin synthesis gene cluster, is possibly responsible for the increase in salinomycin production in a typical strain Streptomyces albus DSM41398. Conclusively, a tentative regulatory model of ribosome engineering combined with ARTP in S. ablus is proposed to explore the roles of transcriptional regulators and stringent responses in the biosynthesis regulation of salinomycin.

SUBMITTER: Zhang K

PROVIDER: S-EPMC6733881 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Combinatorial Effect of ARTP Mutagenesis and Ribosome Engineering on an Industrial Strain of <i>Streptomyces albus</i> S12 for Enhanced Biosynthesis of Salinomycin.

Zhang Kuipu K Mohsin Ali A Dai Yichen Y Chen Zhongbing Z Zhuang Yingping Y Chu Ju J Guo Meijin M

Frontiers in bioengineering and biotechnology 20190903

Salinomycin, an important polyketide, has been widely utilized in agriculture to inhibit growth of pathogenic bacteria. In addition, salinomycin has great potential in treatment of cancer cells. Due to inherited characteristics and beneficial potential, its demand is also inclining. Therefore, there is an urgent need to increase the current high demand of salinomycin. In order to obtain a high-yield mutant strain of salinomycin, the present work has developed an efficient breeding process of <i> ...[more]

PMID: 31552238

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Project description:Streptomyces is well known for biosynthesis of secondary metabolites with diverse bioactivities. Although oils have been employed as carbon sources to produce polyketide antibiotics for several industrial Streptomyces strains, the intrinsic correlation between oil utilization and high production of antibiotics still remains unclear. In this study, we investigated the correlation between oil metabolism and salinomycin biosynthesis in Streptomyces albus ZD11, which employs soybean oil as the main carbon source. Comparative genomic analysis revealed the enrichment of genes related to triacylglycerol (TAG) metabolism in S. albus ZD11. Transcriptomic profiling further confirmed the enhancement of TAG metabolism and acyl coenzyme A biosynthesis in S. albus ZD11. Multiple secreted lipases, which catalyze TAG hydrolysis, were seen to be working in a synergistic and complementary manner in aiding the efficient and stable hydrolyzation of TAGs. Together, our results suggest that enhanced TAG hydrolysis and fatty acid degradation contribute to the high efficiency of oil utilization in S. albus ZD11 in order to provide abundant carbon precursors for cell growth and salinomycin biosynthesis.IMPORTANCE In order to obtain high-level production of antibiotics, oils have been used as the main carbon source for some Streptomyces strains. Based on multiomics analysis, this study provides insight into the relationship between triacylglycerol (TAG) metabolism and antibiotic biosynthesis in S. albus ZD11, an oil-preferring industrial Streptomyces strain. Our investigation into TAG hydrolysis yielded further evidence that this strain utilizes complicated strategies enabling an efficient TAG metabolism. In addition, a novel secreted lipase was identified that exhibited highly hydrolytic activity for medium- and long-chain TAGs. Our findings represent a good start toward clarifying the complicated relationship between TAG catabolism and high-level antibiotic production in the industrial strains.

Dataset Information

Combinatorial Effect of ARTP Mutagenesis and Ribosome Engineering on an Industrial Strain of Streptomyces albus S12 for Enhanced Biosynthesis of Salinomycin.

Publications

Combinatorial Effect of ARTP Mutagenesis and Ribosome Engineering on an Industrial Strain of <i>Streptomyces albus</i> S12 for Enhanced Biosynthesis of Salinomycin.

Similar Datasets

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