A mutant strain of Streptomyces venezuelae was engineered by deletion of the entire gene cluster related to biosynthesis of the endogenous deoxysugar (TDP-D-desosamine) and replacement with genes required for biosynthesis of an intermediate sugar (TDP-4-keto-6-deoxy-D-glucose) or an exogenous sugar (TDP-D-olivose), from the oleandomycin and urdamycin deoxysugar pathways. The 'sugar-flexible' glycosyltransferase (DesVII) was able to attach the intermediate sugar and the new sugar to both 12- and 14-membered macrolactones thus producing quinovose or olivose glycosylated 10-deoxymethynolide and narbonolide, respectively. In addition, hydroxylated analogs of the new metabolites were detected. These results demonstrate a successful attempt of engineering the deoxysugar pathway for generation of novel hybrid macrolide antibiotics.
This study examined the structural variables affecting the environmental effects of organic farming compared to those of conventional farming. A meta-analysis based on 107 studies and 360 observations published from 1977 to 2012 compared energy efficiency (EE) and greenhouse gas emissions (GHGE) for organic and conventional farming. The meta-analysis systematically analyzed the results of earlier comparative studies and used logistic regression to identify the structural variables that contributed to differences in the effects of organic and conventional farming on the environment. The statistical evidence identified characteristics that differentiated the environmental effects of organic and conventional farming, which is controversial. The results indicated that data sources, sample size and product type significantly affected EE, whereas product type, cropping pattern and measurement unit significantly affected the GHGE of organic farming compared to conventional farming. Superior effects of organic farming on the environment were more likely to appear for larger samples, primary data rather than secondary data, monocropping rather than multicropping, and crops other than fruits and vegetables. The environmental effects of organic farming were not affected by the study period, geographic location, farm size, cropping pattern, or measurement method.
Bacterial integration host factors (IHFs) play important roles in site-specific recombination, DNA replication, transcription, genome organization and bacterial pathogenesis. In Streptomyces coelicolor, there are three putative IHFs: SCO1480, SCO2950 and SCO5556. SCO1480 or Streptomyces IHF (sIHF) was previously identified as a transcription factor that binds to the promoter region of redD, the pathway-specific regulatory gene for the undecylprodigiosin biosynthetic gene cluster. Here we show that production of the pigmented antibiotics actinorhodin and undecylprodigiosin is strongly enhanced in sihf null mutants, while sporulation was strongly inhibited, with an on average 25% increase in spore size. Furthermore, the sihf mutant spores showed strongly reduced viability, with high sensitivity to heat and live/dead staining revealing a high proportion of empty spores, while enhanced expression of sIHF increased viability. This suggests a major role for sIHF in controlling viability, perhaps via the control of DNA replication and/or segregation. Proteomic analysis of the sihf null mutant identified several differentially expressed transcriptional regulators, indicating that sIHF may have an extensive response regulon. These data surprisingly reveal that a basic architectural element conserved in many actinobacteria such as mycobacteria, corynebacteria, streptomycetes and rhodococci may act as a global regulator of secondary metabolism and cell development.
γ-Butyrolactones in Streptomyces are well recognized as bacterial hormones, and they affect secondary metabolism of Streptomyces. γ-Butyrolactone receptors are considered important regulatory proteins, and various γ-butyrolactone synthases and receptors have been reported in Streptomyces. Here, we characterized a new regulator, SCO0608, that interacted with SCB1 (γ-butyrolactone of Streptomyces coelicolor) and bound to the scbR/A and adpA promoters. The SCO0608 protein sequences are not similar to those of any known γ-butyrolactone binding proteins in Streptomyces such as ScbR from S. coelicolor or ArpA from Streptomyces griseus. Interestingly, SCO0608 functions as a repressor of antibiotic biosynthesis and spore formation in R5 complex media. We showed the existence of another type of γ-butyrolactone receptor in Streptomyces, and this SCO0608 was named ScbR-like γ-butyrolactone binding regulator (SlbR) in S. coelicolor.
Streptomyces, which produces many pharmaceutical antibiotics and anticancer agents, is a genus of soil-dwelling bacteria with numerous regulators that control both primary and secondary metabolism. NdgR is highly conserved in Streptomyces spp. and is known to be involved in antibiotic production, tolerance against shock and physical stress, nitrogen metabolism, leucine metabolism, and N-acetylglucosamine metabolism. As another function of NdgR, we report the involvement of NdgR in glycerol metabolism in S. coelicolor. Initially, a glycerol utilization operon containing gylCABX was found to be up-regulated in an ndgR deletion mutant (BG11) grown in N-acetylglucosamine solid minimal media compared with wild-type strain (M145). BG11 produced more antibiotics with a small amount of glycerol and increased glycerol utilization, yielding higher concentrations of lactate and acetate per cell. Moreover, fatty acid production was also changed in BG11 to produce longer chain fatty acids, phenolic compounds, alkanes, and fatty alcohols. Using a gel retardation assay, NdgR was found to bind the upstream region of gylC, working as a repressor. NdgR is a second regulator of a glycerol utilization operon, for which only one regulator, GylR was previously known.
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