Protein misfolding in the endoplasmic reticulum (ER) activates a set of intracellular signaling pathways, collectively termed the Unfolded Protein Response (UPR). UPR signaling promotes cell survival by reducing misfolded protein levels. If homeostasis cannot be restored, UPR signaling promotes cell death. The molecular basis for the switch between prosurvival and proapoptotic UPR function is poorly understood. The ER-resident proteins, PERK and IRE1, control two key UPR signaling pathways. Protein misfolding concomitantly activates PERK and IRE1 and has clouded insight into their contributions toward life or death cell fates. Here, we employed chemical-genetic strategies to activate individually PERK or IRE1 uncoupled from protein misfolding. We found that sustained PERK signaling impaired cell proliferation and promoted apoptosis. By contrast, equivalent durations of IRE1 signaling enhanced cell proliferation without promoting cell death. These results demonstrate that extended PERK and IRE1 signaling have opposite effects on cell viability. Differential activation of PERK and IRE1 may determine life or death decisions after ER protein misfolding.

§ Previous signs and symptoms included one or more of the following: fever (temperature >99.5°F [37.5°C]), cough, shortness of breath, myalgias, sore throat, vomiting, diarrhea, change in or loss of taste, change in or loss of smell, chest tightness.

A nonribosomal peptide synthetase (NRPS) gene cluster (sfa) was identified in Streptomyces thioluteus to direct the biosynthesis of the diisonitrile antibiotic SF2768. Its biosynthetic pathway was reasonably proposed based on bioinformatics analysis, metabolic profiles of mutants, and the elucidation of the intermediate and shunt product structures. Bioinformatics-based alignment found a putative ATP-binding cassette (ABC) transporter related to iron import within the biosynthetic gene cluster, which implied that the product might be a siderophore. However, characterization of the metal-binding properties by high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), metal-ligand titration, thin-layer chromatography (TLC), and chrome azurol S (CAS) assays revealed that the final product SF2768 and its diisonitrile derivatives specifically bind copper, rather than iron, to form stable complexes. Inductively coupled plasma mass spectrometry (ICP-MS) analysis revealed that the intracellular cupric content of S. thioluteus significantly increased upon incubation with the copper-SF2768 complex, direct evidence for the copper acquisition function of SF2768. Further in vivo functional characterization of the transport elements for the copper-SF2768 complexes not only confirmed the chalkophore identity of the compound but also gave initial clues into the copper uptake mechanism of this nonmethanotrophic microorganism.

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Nature uses four methods of carbon chain elongation for the production of 2-ketoacids, fatty acids, polyketides, and isoprenoids. Using a combination of quantum mechanical (QM) modeling, protein–substrate modeling, and protein and metabolic engineering, we have engineered the enzymes involved in leucine biosynthesis for use as a synthetic “+1” recursive metabolic pathway to extend the carbon chain of 2-ketoacids. This modified pathway preferentially selects longer-chain substrates for catalysis, as compared to the non-recursive natural pathway, and can recursively catalyze five elongation cycles to synthesize bulk chemicals, such as 1-heptanol, 1-octanol, and phenylpropanol directly from glucose. The “+1” chemistry is a valuable metabolic tool in addition to the “+5” chemistry and “+2” chemistry for the biosynthesis of isoprenoids, fatty acids, or polyketides.

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To investigate the community composition and biogeography of soybean rhizobia in Xinjiang, a total of 151 strains were investigated with RFLP and phylogenetic analyses of 16S rRNA gene, 16S-23S intergenic spacer, three housekeeping genes (atpD, glnII and recA), and two symbiotic genes (nifH and nodC), as well as cross-nodulation. Two rhizobial species, Bradyrhizobium liaoningense and Sinorhizobium fredii, were found as dominant groups in communities of soybean rhizobia in Xinjiang, whereas three Rhizobium genomic species, B. yuanmingense and B. japonicum, were minor groups. These genomic species showed clear correlations with eco-regions, and their symbiotic genes were identical or very similar to those of the reference strains for the corresponding species. Conclusively, the dominant soybean rhizobia S. fredii and B. liaoningense in Xinjiang might be introduced from other Chinese regions, but they have been selected as the rhizobia adapted to the saline-alkaline soils. The high pH, salinity, and phosphate concentration in soil might be the environmental factors determining the biogeography of these bacteria. It is worth mentioning that a novel Rhizobium species that may have acquired the symbiotic genes from a Bradyrhizobium lineage was identified.

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