Streptomyces cinereoruber strain:NRRL ISP-5012 | isolate:NRRL ISP-5012
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ABSTRACT:
PROVIDER: PRJNA581031 | ENA |
REPOSITORIES: ENA
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Project description:Streptomyces tsukubaensis NRRL 18488 is the preferred strain for the production of immunosuppressant agent tacrolimus (FK506). To take full advantage of its genetic potential, systematic understanding of secondary metabolism and related regulatory mechanisms is highly demanded. Here, to this end, we complete its 7.9 Mbp linear genome sequence followed by integrating with multi-omics measurements. With accurate reannotation of FK506 gene cluster, total 2,389 transcription start sites were determined by using primary transcriptome analysis. Integrated analysis of transcriptome and translatome data revealed that secondary metabolic gene clusters, especially FK506 cluster, undergo translational control with decrease in translational efficiency according to the growth. Furthermore, we demonstrated that SD motif has little correlation with ribosome pausing but AT-rich codons delay the translational elongation. Strong ribosome pausing was observed in the rare TTA codon in FK506 cluster. This comprehensive genome-scale analysis provides insight to the translational regulation of secondary metabolism in S. tsukubaensis.
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Project description:Epidemiologic studies demonstrate that women from cultures that consume high levels of dietary soy have reduced breast cancer rates compared to women from cultures where soy consumption is typically much lower. The types of soy products consumed can also differ with Asian cultures consuming primarily minimally refined soy products while Western cultures often consume more highly refined soy products such as isolated soy protein (ISP). Our previous work showed that lifetime exposure to a diet containing 20% ISP promoted mammary tumor development in MTB-IGFIR transgenic mice. In this study, lifetime exposure to lower levels of ISP were evaluated (5% ISP and 1% ISP) to determine whether more moderate levels of ISP could protect against mammary tumorigenesis. A standard rodent diet, Teklad 2018 was also included in this study and Teklad 2018 contains a less refined form of soy, namely soybean meal. MTB-IGFIR mice fed ISP diets, independent of the concentration, displayed increased mammary tumor incidence and reduced tumor latency compared to MTB-IGFIR mice fed a 20% casein diet. Unexpectedly, MTB-IGFIR mice fed Teklad 2018 were completely protected against mammary tumor development. Although RNA sequencing of mammary tumors from ISP or casein fed mice did not identified gene expression patterns associated with the ISP diets, the ISP diets consistently promoted the expression of contractile related proteins in pubertal mammary glands. Therefore, lifetime exposure to ISP may alter gene expression in pubertal mammary glands rendering them more susceptible to transformation. Based on these findings women may want to avoid highly refined soy products such as ISP and switch to less refined forms of dietary soy until additional studies can be performed.
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Project description:Epidemiologic studies demonstrate that women from cultures that consume high levels of dietary soy have reduced breast cancer rates compared to women from cultures where soy consumption is typically much lower. The types of soy products consumed can also differ with Asian cultures consuming primarily minimally refined soy products while Western cultures often consume more highly refined soy products such as isolated soy protein (ISP). Our previous work showed that lifetime exposure to a diet containing 20% ISP promoted mammary tumor development in MTB-IGFIR transgenic mice. In this study, lifetime exposure to lower levels of ISP were evaluated (5% ISP and 1% ISP) to determine whether more moderate levels of ISP could protect against mammary tumorigenesis. A standard rodent diet, Teklad 2018 was also included in this study and Teklad 2018 contains a less refined form of soy, namely soybean meal. MTB-IGFIR mice fed ISP diets, independent of the concentration, displayed increased mammary tumor incidence and reduced tumor latency compared to MTB-IGFIR mice fed a 20% casein diet. Unexpectedly, MTB-IGFIR mice fed Teklad 2018 were completely protected against mammary tumor development. Although RNA sequencing of mammary tumors from ISP or casein fed mice did not identified gene expression patterns associated with the ISP diets, the ISP diets consistently promoted the expression of contractile related proteins in pubertal mammary glands. Therefore, lifetime exposure to ISP may alter gene expression in pubertal mammary glands rendering them more susceptible to transformation. Based on these findings women may want to avoid highly refined soy products such as ISP and switch to less refined forms of dietary soy until additional studies can be performed.
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