Pactamycin, a structurally unique aminocyclitol natural product isolated from Streptomyces pactum, has potent antibacterial, anti-tumor and anti-protozoa activities. However, its production yields under currently used culture conditions are generally low. To understand how pactamycin biosynthesis is regulated and explore the possibility of improving pactamycin production in S. pactum, we investigated the transcription regulations of pactamycin biosynthesis. In vivo inactivation of two putative pathway-specific regulatory genes, ptmE and ptmF, resulted in mutant strains that are not able to produce pactamycin. Genetic complementation using a cassette containing ptmE and ptmF integrated into the S. pactum chromosome rescued the production of pactamycin. Transcriptional analysis of the ΔptmE and ΔptmF strains suggests that both genes control the expression of the whole pactamycin biosynthetic gene cluster. However, attempts to overexpress these regulatory genes by introducing a second copy of the genes in S. pactum did not improve the production yield of pactamycin. We discovered that pactamycin biosynthesis is sensitive to phosphate regulation. Concentration of inorganic phosphate higher than 2 mM abolished both the transcription of the biosynthetic genes and the production of the antibiotic. Draft genome sequencing of S. pactum and bioinformatics studies revealed the existence of global regulatory genes, e.g., genes that encode a two-component PhoR-PhoP system, which are commonly involved in secondary metabolism. Inactivation of phoP did not show any significant effect to pactamycin production. However, in the phoP::aac(3)IV mutant, pactamycin biosynthesis is not affected by external inorganic phosphate concentration.
Pseudo-oligosaccharides are microbial-derived secondary metabolites whose chemical structures contain pseudosugars (glycomimetics). Due to their high resemblance to the molecules of life (carbohydrates), most pseudo-oligosaccharides show significant biological activities. Some of them have been used as drugs to treat human and plant diseases. Because of their significant economic value, efforts have been put into understanding their biosynthesis, optimizing their fermentation conditions, and engineering their metabolic pathways to obtain better production yields. A number of unusual enzymes participating in diverse biosynthetic pathways to pseudo-oligosaccharides have been reported. Various methods and conditions to improve the production yields of the target compounds and eliminate byproducts have also been developed. This review article describes recent studies on the biosynthesis, fermentation optimization, and metabolic engineering of high-value pseudo-oligosaccharides.
We statistically analyzed 31 published studies comprising 113 water samples collected from 17 countries for SARS-CoV-2 positivity. The pooled estimated prevalence of viral RNA in the tested samples was 64.1% [95% CI:51.6%, 74.9%] with considerable heterogeneity (I2: 90.1%, P<0.001). Notably, wastewater, sewage, hospital septic-tank, biological sludge, and effluent demonstrated statistical significance (P<0.05) for RNA positivity. The country-wise pooled estimated prevalence for Germany, India, Turkey, Spain, the Netherlands, Italy, the USA, and Japan were 88% (76%, 94%), 85% (33%, 98%), 83% (43%, 97%), 78% (54%, 92%), 60% (41%, 77%), 53% (36%, 70%), 53% (27%, 77%), and 25% (13%,43%), respectively. Further subgroup analyses showed that the prevalence of SARS-CoV-2 among the tested water samples was significantly higher in middle-income countries compared to high-income groups. Our data, therefore, suggests wastewater-based epidemiological surveillance as an important tool for community-wide monitoring of SARS-CoV-2. Doi: 10.28991/SciMedJ-2022-04-03-02 Full Text: PDF
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